Canadian Journal Of Physiology And Pharmacology[JOURNAL]
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200 papers
Sex-specific considerations in cardiovascular drug therapy.
Rabinovich-Nikitin I, Liu S, Kirshenbaum LA
Can J Physiol Pharmacol · 2024 Sep · PMID 38781601 · Publisher ↗
Despite major advances in cardiac research over the past three decades, cardiovascular disease (CVD) still remains the leading cause of morbidity and mortality in women and men worldwide. However, a major challenge for h...
Despite major advances in cardiac research over the past three decades, cardiovascular disease (CVD) still remains the leading cause of morbidity and mortality in women and men worldwide. However, a major challenge for health care providers is that the current guidelines for cardiovascular drug therapies do not consider the impact of sex in the development of treatment plan for optimizing therapies for women. Clinical research in recent years suggests significant pharmacological and pharmacokinetic differences between females and males, which have been attributed in part to differences in body composition, plasma protein binding capacity, drug metabolism, and excretion. Herein, we provide a comprehensive review regarding sex-specific differences and drugs commonly used for CVDs in women and men. Understanding how sex-related differences influence drug efficacy and CVD outcomes is crucial for not only optimizing treatment strategies for women and men but also to encourage the implementation of specific guidelines that address sex difference as a consideration for the treatment of CVDs.
Chloramphenicol alleviates 5-fluorouracil-induced cellular senescence through activation of autophagy.
Bai S, Zhao Q, Jia H … +2 more , He F, Wang X
Can J Physiol Pharmacol · 2024 Nov · PMID 38776555 · Publisher ↗
5-Fluorouracil (5-FU) is a first-line treatment for colorectal cancer, but side effects such as severe diarrhea are common in clinical use and have been linked to its induction of normal cell senescence. Chloramphenicol...
5-Fluorouracil (5-FU) is a first-line treatment for colorectal cancer, but side effects such as severe diarrhea are common in clinical use and have been linked to its induction of normal cell senescence. Chloramphenicol (CAP) is an antibiotic commonly used to treat typhoid or anaerobic infections, but its senescence-related aspects have not been thoroughly investigated. Here, we used 5-FU to induce senescence in human umbilical vein endothelial cells (HUVECs) and investigated the relationship between CAP and cellular senescence at the cellular level. In a model of cellular senescence induced by 5-FU treatment, we discovered that CAP treatment reversed the rise in the percentage of senescence-associated galactosidase (SA-β-gal)-positive cells and decreased the expression of senescence-associated proteins (p16), senescence-associated genes (p21), and senescence-associated secretory phenotypes (SASPs: IL-6, TNF-α). In addition, CAP subsequently restored the autophagic process inhibited by 5-FU and upregulated the levels of autophagy-related proteins. Mechanistically, we found that CAP restored autophagic flux by inhibiting the mTOR pathway, which in turn alleviated FU-induced cellular senescence. Our findings suggest that CAP may help prevent cellular senescence and restore autophagy, opening up new possibilities and approaches for the clinical management of colorectal cancer.
Cardiovascular and physiological risk factors in women at mid-life and beyond.
Rodriguez de Morales YA, Abramson BL
Can J Physiol Pharmacol · 2024 Aug · PMID 38739947 · Publisher ↗
Cardiovascular disease (CVD) is the leading cause of death in women. After menopause, sex-specific and gender-specific factors may play an important role in increasing CVD risk, with changes in sex hormones, body fat dis...
Cardiovascular disease (CVD) is the leading cause of death in women. After menopause, sex-specific and gender-specific factors may play an important role in increasing CVD risk, with changes in sex hormones, body fat distribution, lipid and metabolic profile, and structural and functional vascular modifications. Premature and early-onset menopause are detrimental to cardiovascular health due to the early cessation of the protective effect of endogenous estrogen. An independent association of menopause with an increased risk of CVD has been documented in early menopause (<45 years). Sex-related differences are relevant in pharmacokinetics and pharmacodynamics; different enzyme formations, drug compatibility, efficacy, and side effects vary for different sexes. Despite some progress in sex and gender research in CVD, disparities remain. Menopausal hormone therapy (MHT) is available at mid-life for symptoms of menopause and may impact cardiovascular risk. Taken early, MHT may reduce CVD morbimortality. However, this is balanced against the risk of increased thrombosis. This paper reviews physiologic changes that contribute to cardiovascular risk in postmenopausal women and discusses clinical implications. Specifically, it explores the atheroprotective effects of estrogen and MHT and the associations between menopause with lipid levels, hypertension, body composition, and diabetes for women at mid-life and beyond.
Agonists, inverse agonists, and antagonists as therapeutic approaches to manipulate retinoic acid-related orphan receptors.
Nematisouldaragh D, Nguyen H, Rabinovich-Nikitin I
Can J Physiol Pharmacol · 2024 Nov · PMID 38728749 · Publisher ↗
Retinoic acid-related orphan receptors (RORs) serve as transcription factors that play a pivotal role in a myriad of physiological processes within the body. Their involvement extends to critical biological processes tha...
Retinoic acid-related orphan receptors (RORs) serve as transcription factors that play a pivotal role in a myriad of physiological processes within the body. Their involvement extends to critical biological processes that confer protective effects in the heart, immune system, and nervous system, as well as contributing to the mitigation of several aggressive cancer types. These protective functions are attributed to ROR's regulation of key proteins and the management of various cellular processes, including autophagy, mitophagy, inflammation, oxidative stress, and glucose metabolism, highlighting the emerging need for pharmacological approaches to modulate ROR expression. Thus, the modulation of RORs is a rapidly growing area of research aimed not only at comprehending these receptors, but also at manipulating them to attain the desired physiological response. Despite the presence of natural ROR ligands, the development of synthetic agonists with high selectivity for these receptors holds substantial therapeutic potential. The exploration and advancement of such compounds can effectively target diseases associated with ROR dysregulation, thereby providing avenues for therapeutic interventions. Herein, we provide a comprehensive examination of the multifaceted role of ROR in diverse physiological and pathophysiological conditions, accompanied by an in-depth exploration of a spectrum of ROR agonists, inverse agonists, and antagonists.
Coronary microvascular disease in women: epidemiology, mechanisms, evaluation, and treatment.
Steinberg RR, Dragan A, Mehta PK … +1 more , Toleva O
Can J Physiol Pharmacol · 2024 Oct · PMID 38728748 · Publisher ↗
Coronary microvascular dysfunction (CMD) involves functional or structural abnormalities of the coronary microvasculature resulting in dysregulation of coronary blood flow (CBF) in response to myocardial oxygen demand. T...
Coronary microvascular dysfunction (CMD) involves functional or structural abnormalities of the coronary microvasculature resulting in dysregulation of coronary blood flow (CBF) in response to myocardial oxygen demand. This perfusion mismatch causes myocardial ischemia, which manifests in patients as microvascular angina (MVA). CMD can be diagnosed non-invasively via multiple imaging techniques or invasively using coronary function testing (CFT), which assists in determining the specific mechanisms involving endothelium-independent and dependent epicardial and microcirculation domains. Unlike traditional coronary artery disease (CAD), CMD can often occur in patients without obstructive atherosclerotic epicardial disease, which can make the diagnosis of CMD difficult. Moreover, MVA due to CMD is more prevalent in women and carries increased risk of future cardiovascular events. Successful treatment of symptomatic CMD is often patient-specific risk factor and endotype targeted. This article aims to review newly identified mechanisms and novel treatment strategies for managing CMD, and outline sex-specific differences in the presentation and pathophysiology of the disease.
Cytochrome P450 1B1 is critical in the development of TNF-α, IL-6, and LPS-induced cellular hypertrophy.
ElKhatib MAW, Gerges SH, Isse FA … +1 more , El-Kadi AOS
Can J Physiol Pharmacol · 2024 Jul · PMID 38701513 · Publisher ↗
Heart failure (HF) is preceded by cellular hypertrophy (CeH) which alters expression of cytochrome P450 enzymes (CYPs) and arachidonic acid (AA) metabolism. Inflammation is involved in CeH pathophysiology, but mechanisms...
Heart failure (HF) is preceded by cellular hypertrophy (CeH) which alters expression of cytochrome P450 enzymes (CYPs) and arachidonic acid (AA) metabolism. Inflammation is involved in CeH pathophysiology, but mechanisms remain elusive. This study investigates the impacts of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and lipopolysaccharides (LPS) on the development of CeH and the role of CYP1B1. AC16 cells were treated with TNF-α, IL-6, and LPS in the presence and absence of CYP1B1-siRNA or resveratrol. mRNA and protein expression levels of CYP1B1 and hypertrophic markers were determined using PCR and Western blot analysis, respectively. CYP1B1 enzyme activity was determined, and AA metabolites were analyzed using liquid chromatography-tandem mass spectrometry. Our results show that TNF-α, IL-6, and LPS induce expression of hypertrophic markers, induce CYP1B1 expression, and enantioselectively modulate CYP1B1-mediated AA metabolism in favor of mid-chain HETEs. CYP1B1-siRNA or resveratrol ameliorated these effects. In conclusion, our results demonstrate the crucial role of CYP1B1 in TNF-α, IL-6, and LPS-induced CeH.
Unraveling the molecular landscape of kAE1: a narrative review.
Mungara P, Waiss M, Hartwig S … +2 more , Burger D, Cordat E
Can J Physiol Pharmacol · 2024 Jul · PMID 38669699 · Publisher ↗
Kidney anion exchanger 1 (kAE1) is an isoform of the AE1 protein encoded by the gene. It is a basolateral membrane protein expressed by α-intercalated cells in the connecting tubules and collecting duct of the kidney. I...
Kidney anion exchanger 1 (kAE1) is an isoform of the AE1 protein encoded by the gene. It is a basolateral membrane protein expressed by α-intercalated cells in the connecting tubules and collecting duct of the kidney. Its main function is to exchange bicarbonate and chloride ions between the blood and urine to maintain blood pH at physiological threshold. The kAE1 protein undergoes multiple post-translational modifications such as phosphorylation and ubiquitination and interacts with many different proteins such as claudin-4 and carbonic anhydrase II. Mutations in the gene may lead to the development of distal renal tubular acidosis, characterized by the failure to acidify the urine, which may result in nephrocalcinosis and in more severe cases, renal failure. In this review, we discuss the structure and function of kAE1, its post-translational modifications, and protein-protein interactions. Finally, we discuss insights gained from the study of kAE1 mutations in humans and in mice.
Low-fat cheese ameliorates glucose intolerance and normalizes insulin secretion in a rat model of type 2 diabetes by promoting β-cell recovery.
Hanning ARZ, Hassanabad MF, Hashemi Z … +2 more , Wang X, Chan CB
Can J Physiol Pharmacol · 2024 Jul · PMID 38669698 · Publisher ↗
We aimed to determine if cheese could reduce glucose intolerance in aged rats with overt type 2 diabetes (T2D). Male Sprague-Dawley rats treated with high-fat diet (HFD) and streptozotocin (STZ) to elicit T2D were hyperg...
We aimed to determine if cheese could reduce glucose intolerance in aged rats with overt type 2 diabetes (T2D). Male Sprague-Dawley rats treated with high-fat diet (HFD) and streptozotocin (STZ) to elicit T2D were hyperglycemic. One week after STZ injection, low-fat (LOW) or regular-fat (REG) cheese was provided for 5 weeks and compared with T2D and low-fat diet reference (REF) groups. Food intake and weight gain were similar in all groups. Oral glucose tolerance tests revealed glucose intolerance in T2D rats that was partially ameliorated by LOW but not REG. Insulin secretion during the oral glucose tolerance test was impaired in T2D and REG at 10 min ( < 0.05) but the iAUC was highly variable in all groups and statistical differences were not detected ( > 0.05). β-cell mass and pancreatic insulin content in T2D and REG were 50% lower than REF ( < 0.05), whereas LOW was not significantly different. Although isolated islets from all groups responded to glucose, the absolute amount of insulin secreted by T2D and REG was markedly reduced compared with REF, while LOW islets had relatively normal secretion. In conclusion, LOW but not REG cheese enhanced β-cell recovery from HFD/STZ treatment that led to amelioration of glucose tolerance within 5 weeks.
Cardiogenic shock-sex-specific risk factors and outcome differences.
Zhang H, Shah A, Ravandi A
Can J Physiol Pharmacol · 2024 Sep · PMID 38663027 · Publisher ↗
Cardiogenic shock (CS) remains a high-mortality condition despite technological and therapeutic advances. One key to potentially improving CS prognosis is understanding patient heterogeneity and which patients may benefi...
Cardiogenic shock (CS) remains a high-mortality condition despite technological and therapeutic advances. One key to potentially improving CS prognosis is understanding patient heterogeneity and which patients may benefit most from different treatment options, a key element of which is sex differences. While cardiovascular diseases (CVDs) have historically been considered a male-dominant condition, the field is increasingly aware that females are also a substantial portion of the patient population. While estrogen has been implicated in protective roles against CVD and tissue hypoxia, its role in CS remains unclear. Clinically, female CS patients tend to be older, have more severe comorbidities and are more likely to have non-acute myocardial infarction etiologies with preserved ejection fractions. Female CS patients are more likely to receive pharmacotherapy while less likely to receive mechanical circulatory support. There is increased short-term mortality in females, although long-term mortality is similar between the sexes. More sex-specific and age-stratified research needs to be done to fully understand the relevant pathophysiological differences in CS, to better recognize and manage CS patients and reduce its mortality.
Discontinuing semaglutide after weight loss: strategy for weight maintenance and a possible new side effect.
Carris NW, Wallace S, DuCoin CG … +3 more , Mhaskar R, Stern M, Bunnell B
Can J Physiol Pharmacol · 2024 Jun · PMID 38587178 · Publisher ↗
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) facilitate weight loss. Weight regain off therapy is concerning. We reported the case of a 35-year-old male prescribed oral semaglutide with 22.7 kg weight loss over...
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) facilitate weight loss. Weight regain off therapy is concerning. We reported the case of a 35-year-old male prescribed oral semaglutide with 22.7 kg weight loss over 120 days. Herein, we describe the clinical course when discontinuing GLP-1 RA therapy, one approach to maintaining weight loss after discontinuation, and a possible new side effect. At day 120, we continued oral semaglutide 7 mg daily, down from 14 mg, for weight maintenance with subsequent weight regain. We re-increased semaglutide to 14 mg/day with weight re-loss within 1 month and weight maintance for a year. We then discontinued semaglutide; weight loss was maintained for 6 months. The patient reported lactose intolerance ∼13 months before starting semaglutide. During semaglutide therapy, the patient reported worsened lactose intolerance and new gluten intolerance. Food allergy/celiac testing were negative. Intolerances did not improve with semaglutide discontinuation. Six months after semaglutide discontinuation, the patient was diagnosed with small intestinal bacterial overgrowth, possibly worsened by semaglutide. Factors potentially supporting weight maintenance were early drug treatment for new-onset obesity, non-geriatric age, strength training, and diet modification. The case highlights tailoring approaches to maintain weight loss without GLP-1 RAs. Trials are needed to optimize weight maintenance strategies.
Psychological interventions targeting mental health and stress among females with cardiac disease: a scoping review.
Susinski S, Bouchard K, Stragapede E … +3 more , Dozois S, Sterling E, Tulloch H
Can J Physiol Pharmacol · 2024 Oct · PMID 38587177 · Publisher ↗
Interventions that target mental health symptoms and stress among those with established cardiac disease have included predominately male samples despite female patients reporting greater severity of these symptoms. The...
Interventions that target mental health symptoms and stress among those with established cardiac disease have included predominately male samples despite female patients reporting greater severity of these symptoms. The aim of this scoping review was to synthesize the published literature on psychological interventions for females with cardiac disease. We conducted a systematic search of peer-reviewed randomized clinical trials (RCTs) published in the English language from 2003 to 2023, in three databases: Medline (Ovid), PsycInfo (Ovid), and CINAHL (EBSCO). Articles that included female samples, a control or comparison group, implemented psychological interventions, and measured depression, anxiety, or stress as an outcome were included in the review. Nine articles describing eight RCTs of psychological interventions, with a total of 1587 female patients with cardiac disease, were included. Interventions were most successful at reducing stress (75% of studies measuring stress reported efficacy), while symptoms of depression and anxiety were less responsive to intervention (∼30% of studies targeting these symptoms reported improvements) in comparison to a control condition. This scoping review highlights that further advancement in knowledge is required to better address the needs of females with cardiac disease and distress, particularly depression and anxiety.
Sex-specific effects of frailty on cardiac structure and function: insights from preclinical models.
Bisset ES, Howlett SE
Can J Physiol Pharmacol · 2024 Aug · PMID 38489788 · Publisher ↗
Advanced age is an independent risk factor for cardiovascular diseases in both sexes. This is thought to be due, in part, to age-dependent cellular, structural, and functional changes in the heart, a process known as car...
Advanced age is an independent risk factor for cardiovascular diseases in both sexes. This is thought to be due, in part, to age-dependent cellular, structural, and functional changes in the heart, a process known as cardiac aging. An emerging view is that cardiac aging leads to the accumulation of cellular and subcellular deficits that increase susceptibility to cardiovascular diseases. Still, people age at different rates, with those aging rapidly considered frail. Evidence suggests that frailty, rather than simply age, is a major risk factor for cardiovascular disease and predicts adverse outcomes in those affected. Recent studies in mouse models of frailty show that many adverse changes associated with cardiac aging are more prominent in mice with a high degree of frailty. This suggests that frailty sets the stage for late life cardiovascular diseases to flourish and raises the possibility that treating frailty may treat cardiovascular diseases. These studies show that ventricular dysfunction increases with frailty in males only, whereas atrial dysfunction increases with frailty in both sexes. These results may shed light on the reasons that men and women can be susceptible to different cardiovascular diseases as they age, and why frail individuals are especially vulnerable to these disorders.
Cardio-rheumatology: the cardiovascular, pharmacological, and surgical risks associated with rheumatological diseases in women.
Sommer SL, Kontaridis MI
Can J Physiol Pharmacol · 2024 Sep · PMID 38489782 · Full text
Cardiovascular disease (CVD) remains the number one cause of death worldwide. Women are at increased risk of death from CVD, but the mechanisms for how and why this occurs remain elusive. One subset of women who are exce...
Cardiovascular disease (CVD) remains the number one cause of death worldwide. Women are at increased risk of death from CVD, but the mechanisms for how and why this occurs remain elusive. One subset of women who are exceptionally vulnerable to CVD are those with rheumatic diseases (RDs). Indeed, women account for 80% of all RDs, disorders that encompass a broad range of autoimmune and autoinflammatory diseases that lead to chronic inflammation and pathology. The clear association of increased CVD risk in women with RD is thought to be mediated by a number of factors, including RD pathology itself, pharmacological induction of CVD, and/or as yet unidentified mechanisms. As such, elucidation of the causes and treatments of these pathologies has given rise to a new subspecialty of cardiology: cardio-rheumatology. Here, we review and discuss the CVD risks in patients with RDs, the associated sex disparities in RD and CVD care, as well as the current therapeutic and interventional options available to specifically help women with RDs. We hope this discussion will provide guidance and support to patients, as well as to cardio-rheumatologists, as these groups are the most uniquely positioned to radically improve CVD care in these individuals. Moreover, we are hopeful this discussion may lead to better, more efficacious approaches to treating these disorders in women in the near future.
HFpEF and sex: understanding the role of sex differences.
Smereka Y, Ezekowitz JA
Can J Physiol Pharmacol · 2024 Aug · PMID 38447124 · Publisher ↗
Heart failure is a complex clinical syndrome with many etiological factors and complex pathophysiology affecting millions worldwide. Males and females can have distinct clinical presentation and prognosis, and there is a...
Heart failure is a complex clinical syndrome with many etiological factors and complex pathophysiology affecting millions worldwide. Males and females can have distinct clinical presentation and prognosis, and there is an emerging understanding of the factors that highlight the similarities and differences to synthesize and present available data for sex-specific differences in heart failure with preserved ejection fraction (HFpEF). While the majority of data demonstrate more similarities than differences between females and males in terms of heart failure, there are key differences. Data showed that females have a higher risk of developing HFpEF, but a lower risk of mortality and hospitalization. This can be conditioned by different profiles of comorbidities, postmenopausal changes in sex hormone levels, higher levels of inflammation and chronic microvascular dysfunction in females. These factors, combined with different left ventricular dimensions and function, which are more pronounced with age, lead to a higher prevalence of LV diastolic dysfunction at rest and exercise. As a result, females have lower exercise capacity and quality of life when compared to males. Females also have different activities of systems responsible for drug transformation, leading to different efficacy of drugs as well as higher risk of adverse drug reactions. These data prove the necessity for creating sex-specific risk stratification scales and treatment plans.
Fishing antioxidant 4-hydroxycoumarin derivatives: synthesis, characterization, and in vitro assessments.
Rostom B, Goya-Jorge E, Muro LV … +6 more , Boubrik I, Wiorek S, Karaky R, Kassab I, Rodríguez MEJ, Sylla-Iyarreta Veitía M
Can J Physiol Pharmacol · 2024 Jun · PMID 38447123 · Publisher ↗
Coumarins represent a diverse class of natural compounds whose importance in pharmaceutical and agri-food sectors has motivated multiple novel synthetic derivatives with broad applicability. The phenolic moiety in 4-hydr...
Coumarins represent a diverse class of natural compounds whose importance in pharmaceutical and agri-food sectors has motivated multiple novel synthetic derivatives with broad applicability. The phenolic moiety in 4-hydroxycoumarins underscores their potential to modulate the equilibrium between free radicals and antioxidant species within biological systems. The aim of this work was to assess the antioxidant activity of 18 4-hydroxycoumarin coumarin derivatives, six of which are commercially available and the other 12 were synthesized and chemically characterized and described herein. The 4-hydroxycoumarins were prepared by a two steps synthetic strategy with satisfactory yields. Their antioxidant potential was evaluated through three in vitro methods, two free radical-scavenging assays (DPPH• and ABTS•+) and a metal chelating activity assay. Six synthetic coumarins (, , , , , ) had a scavenging capacity of DPPH• higher than butylated hydroxytoluene (BHT) (IC = 0.58 mmol/L) and compound (4-hydroxy-6-methoxy-2 H-chromen-2-one) with an IC = 0.05 mmol/L outperformed both BHT and ascorbic acid (IC = 0.06 mmol/L). Nine hydroxycoumarins had a scavenging capacity against ABTS•+ greater (, , ) or comparable (, , , , , ) to Trolox (IC = 34.34 µmol/L). Meanwhile, the set had a modest ferrous chelation capacity, but most of them (, , , , , , , , , ) reached up to more than 20% chelating ability percentage. Collectively, this research work provides valuable structural insights that may determine the scavenging and metal chelating activity of 4-hydroxycoumarins. Notably, substitutions at the C6 position appeared to enhance scavenging potential, while the introduction of electron-withdrawing groups showed promise in augmenting chelation efficiency.
Impact of biological sex on valvular heart disease, interventions, and outcomes.
Wiens EJ, Kawa K, Kass M … +1 more , Shah AH
Can J Physiol Pharmacol · 2024 Oct · PMID 38427984 · Publisher ↗
Valvular heart disease (VHD) is common, affecting >14% of individuals aged >75, and is associated with morbidity, including heart failure and arrhythmia, and risk of early mortality. Increasingly, important sex differenc...
Valvular heart disease (VHD) is common, affecting >14% of individuals aged >75, and is associated with morbidity, including heart failure and arrhythmia, and risk of early mortality. Increasingly, important sex differences are being found between males and females with VHD. These sex differences can involve the epidemiology, pathophysiology, presentation, diagnosis, and outcomes of the disease. Females are often disadvantaged, and female sex has been shown to be associated with delayed diagnosis and inferior outcomes in various forms of VHD. In addition, the unique pathophysiologic state of pregnancy is associated with increased risk for maternal and fetal morbidity and mortality in many forms of VHD. Therefore, understanding and recognizing these sex differences, and familiarity with the attendant risks of pregnancy and management of pregnant females with VHD, is of great importance for any primary care or cardiovascular medicine practitioner caring for the female patient. This review will outline sex differences in aortic, mitral, pulmonic, and tricuspid VHD, with particular focus on differences in pathophysiology, clinical presentation, and outcomes. In addition, the pathophysiology and management implications of pregnancy will be discussed.
Epigenetic regulation of sex dimorphism in cardiovascular health.
Thej C, Kishore R
Can J Physiol Pharmacol · 2024 Sep · PMID 38427976 · Full text
Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality, affecting people of all races, ages, and sexes. Substantial sex dimorphism exists in the prevalence, manifestation, and outcomes of CVDs...
Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality, affecting people of all races, ages, and sexes. Substantial sex dimorphism exists in the prevalence, manifestation, and outcomes of CVDs. Understanding the role of sex hormones as well as sex-hormone-independent epigenetic mechanisms could play a crucial role in developing effective and sex-specific cardiovascular therapeutics. Existing research highlights significant disparities in sex hormones, epigenetic regulators, and gene expression related to cardiac health, emphasizing the need for a nuanced understanding of these variations between men and women. Despite these differences, current treatment approaches for CVDs often lack sex-specific considerations. A pivotal shift toward personalized medicine, informed by comprehensive insights into sex-specific DNA methylation, histone modifications, and non-coding RNA dynamics, holds the potential to revolutionize CVD management. By understanding sex-specific epigenetic complexities, independent of sex hormone influence, future cardiovascular research can be tailored to achieve effective diagnostic and therapeutic interventions for both men and women. This review summarizes the current knowledge and gaps in epigenetic mechanisms and sex dimorphism implicated in CVDs.
Tribute-Dr. Pawan K. Singal.
Can J Physiol Pharmacol · 2024 Apr · PMID 38415758 · Publisher ↗
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Cardioprotective effects of losartan and diminazene against the ischemia/reperfusion injury in hyperthyroidism rats.
Pashaei M, Hesari M, Shackebaei D … +1 more , Godini A
Can J Physiol Pharmacol · 2024 Jun · PMID 38377482 · Publisher ↗
Hyperthyroidism is a condition where the thyroid gland produces high levels of thyroid hormone. Heart diseases are one of the main complications of hyperthyroidism. Several studies have shown that losartan (LOS) and dimi...
Hyperthyroidism is a condition where the thyroid gland produces high levels of thyroid hormone. Heart diseases are one of the main complications of hyperthyroidism. Several studies have shown that losartan (LOS) and diminazene aceturate (DIZE) possess cardioprotection effects against cardiac hypertrophy, ischemic heart disease, and heart failure. The research aimed to investigate the cardioprotection of LOS, DIZE, and their combination in the case of levothyroxine (LT4)-induced cardiomyopathy in rats. Hyperthyroidism was induced by LT4 in drinking water (12 mg/L) for 28 days. LOS (10 mg/kg, orally) and/or DIZE (15 mg/kg, subcutaneously) were administrated in rats with hyperthyroidism for 28 days. Decreased serum creatine kinase myoglobin and lactate dehydrogenase levels and cardiac hypertrophy by DIZE and combination therapy in hyperthyroidism rats have been reported. Cardiac hemodynamic findings showed that DIZE and its combination with LOS decreased the LT4-mediated left ventricular developed pressure (LVDP), rate pressure product (RPP), and RPP recovery percentage. Elevated cardiac oxidative stress and inflammation were confirmed by decreasing cardiac superoxide dismutase (SOD) activity and increasing the total oxidative stress and tumor necrosis factor-alpha (TNF-α) levels. SOD activity and TNF-α level were reversed by LOS and DIZE administration, respectively. Generally, DIZE and combination therapy with LOS improved cardiac dysfunction caused by hyperthyroidism in rats, whereas LOS alone has not been able to effectively respond to this dysfunction.
Targeting the vivid facets of apolipoproteins as a cardiovascular risk factor in rheumatoid arthritis.
Sharma A, Sharma C, Sharma L … +10 more , Wal P, Mishra P, Sachdeva N, Yadav S, Vargas De-La Cruz C, Arora S, Subramaniyan V, Rawat R, Behl T, Nandave M
Can J Physiol Pharmacol · 2024 May · PMID 38334084 · Publisher ↗
Mostly, cardiovascular diseases are blamed for casualties in rheumatoid arthritis (RA) patients. Customarily, dyslipidemia is probably the most prevalent underlying cause of untimely demise in people suffering from RA as...
Mostly, cardiovascular diseases are blamed for casualties in rheumatoid arthritis (RA) patients. Customarily, dyslipidemia is probably the most prevalent underlying cause of untimely demise in people suffering from RA as it hastens the expansion of atherosclerosis. The engagement of inflammatory cytokines like tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), etc., is crucial in the progression and proliferation of both RA and abnormal lipid parameters. Thus, lipid abnormalities should be monitored frequently in patients with both primary and advanced RA stages. An advanced lipid profile examination, i.e., direct role of apolipoproteins associated with various lipid molecules is a more dependable approach for better understanding of the disease and selecting suitable therapeutic targets. Therefore, studying their apolipoproteins is more relevant than assessing RA patients' altered lipid profile levels. Among the various apolipoprotein classes, Apo A1 and Apo B are primarily being focused. In addition, it also addresses how calculating Apo B:Apo A1 ratio can aid in analyzing the disease's risk. The marketed therapies available to control lipid abnormalities are associated with many other risk factors. Hence, directly targeting Apo A1 and Apo B would provide a better and safer option.
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