Mousso T, Pham K, Drewes R
… +8 more, Babatunde S, Jong J, Krug A, Inserra G, Biber J, Brazzo JA, Gupte S, Bae Y
Vascul Pharmacol
· 2025 Jun · PMID 40015658
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Aberrant changes in cell behaviors, such as proliferation, apoptosis, and migration, are some of the contributing factors to the development of various cardiovascular diseases (CVDs) and pathologies, including atheroscle...Aberrant changes in cell behaviors, such as proliferation, apoptosis, and migration, are some of the contributing factors to the development of various cardiovascular diseases (CVDs) and pathologies, including atherosclerosis, neointimal hyperplasia, and heart failure. In recent years, numerous studies have identified survivin, a key player in the anti-apoptotic pathway, to be extensively involved in modulating cellular functioning in cancer, with many reaching clinical trials. Though seemingly different, CVDs and cancer share abundant similarities regarding abnormal cell modifications and behaviors. This overlap has sparked growing interest in investigating survivin as a therapeutic target in the context of CVD. With new findings emerging rapidly, a comprehensive understanding of survivin's role in cardiovascular pathology is crucial to revealing its full therapeutic potential and translating these discoveries into effective treatments. This review discusses recent findings of survivin in CVDs and related pathologies, focusing on its dual role in promoting proliferation and inhibiting apoptosis, specifically in atherosclerosis, neointimal hyperplasia, stroke, hypertension, myocardial infarction, and heart failure. Across different cell types and pathological contexts, survivin plays a pivotal role throughout the disease progression-from the onset of disease development to the facilitation of compensatory mechanisms post-injury-primarily through its function in regulating cell proliferation and apoptosis. Furthermore, given the limited research on survivin as a therapeutic target for CVDs, potential clinical avenues, including YM155 (a survivin inhibitor) or adenoviral, adeno-associated, and lentiviral vectors, are also discussed. Overall, this review highlights survivin as a promising target for mitigating the detrimental effects of CVDs and to provide new perspectives to advance research on the intervention of CVDs and associated pathologies.
In recent years, the therapeutic utility of mesenchymal stem cells (MSCs) has received substantial attention from investigators, owing to their pleiotropic properties. The emerging insights from the developments in tissu...In recent years, the therapeutic utility of mesenchymal stem cells (MSCs) has received substantial attention from investigators, owing to their pleiotropic properties. The emerging insights from the developments in tissue engineering provide perspectives for the repair of damaged tissue and the replacement of failing organs. Perivascular cells including MSC-like pericytes, vascular smooth muscles, and other cells located around blood vessels, have been acknowledged to contribute to in situ angiogenesis and repair process. MSCs offer a wide array of therapeutic applications in different pathological states. However, in the current article, we have highlighted the recent updates on MSCs and their key applications in cardiac and cerebrovascular diseases, evident in different preclinical and clinical studies. We believe the present article would assist the investigators in understanding the recent advances of MSCs and exploring their therapeutic potential in varied ailments, especially cardiac and cerebrovascular diseases.
Glycosylation is a post-translational modification in which complex, branched carbohydrates (glycans) are covalently attached to proteins or lipids. Asparagine-link protein (N-) glycosylation is among the most common typ...Glycosylation is a post-translational modification in which complex, branched carbohydrates (glycans) are covalently attached to proteins or lipids. Asparagine-link protein (N-) glycosylation is among the most common types of glycosylation. This process is essential for many biological and cellular functions, and impaired N-glycosylation has been widely implicated in inflammation and cardiovascular diseases. Different technical approaches have been used to increase the coverage of the N-glycome, revealing a high level of complexity of glycans, regarding their structure and attachment site on a protein. In this context, new insights from genomic studies have revealed a genetic regulation of glycosylation, linking genetic variants to total plasma N-glycosylation and N-glycosylation of immunoglobulin G (IgG). In addition, RNAseq approaches have revealed a degree of transcriptional regulation for the glycoenzymes involved in glycan structure. However, our understanding of the association between cardiovascular risk and glycosylation, determined by a complex overlay of genetic and environmental factors, remains limited. Mostly, plasma N-glycosylation profiling in different human cohorts or experimental investigations of specific enzyme functions in models of atherosclerosis have been reported. Most of the uncovered glycosylation associations with pathological mechanisms revolve around the recruitment of inflammatory cells to the vessel wall and lipoprotein metabolism. This review aims to summarise insights from omics studies into the immune and metabolic regulation of N-glycosylation and its association with cardiovascular and metabolic disease risk and to provide mechanistic insights from experimental models. The combination of emerging techniques for glycomics and glycoproteomics with already achieved omics approaches to map the transcriptomic, epigenomic, and metabolomic profile at single-cell resolution will deepen our understanding of the molecular regulation of glycosylation as well as identify novel biomarkers and targets for cardiovascular disease prevention and treatment.
AIMS: Mural cells constitute the outer lining of blood vessels and are essential for vascular development and function. Mural cell loss or malfunction has been associated with numerous diseases including diabetic retinop...AIMS: Mural cells constitute the outer lining of blood vessels and are essential for vascular development and function. Mural cell loss or malfunction has been associated with numerous diseases including diabetic retinopathy, stroke and amyotrophic lateral sclerosis. In this work, we investigate the role of CDC42 in mural cells in vivo, using the developing mouse retina as a model. METHODS: In this study, we generated a mouse model for Cdc42 deletion in mural cells by crossing Pdgfrb-CreER mice with Cdc42flox/flox mice. This model (Cdc42) allowed us to investigate the role of CDC42 in pericytes and smooth muscle cells in the developing and adult retinal vasculature. RESULTS: We find that, during postnatal development, CDC42 is required in both, pericytes and smooth muscle cells to maintain proper cell morphology, mural cell coverage and distribution. During retinal angiogenesis, Cdc42-depleted pericytes lag behind the sprouting front and exhibit decreased proliferation. Consequently, capillaries at the sprouting front remain pericyte deprived, become dilated and are prone to increased vascular leakage. In addition, arteries and arterioles deviate from their normal growth directions and trajectory. While in the adult retina, mural cell coverage normalizes and pericytes adopt a normal morphology, smooth muscle cell morphologies remain abnormal and arteriolar branching angles are markedly reduced. CONCLUSIONS: Our findings demonstrate that CDC42 is required for mural cell migration and proliferation and suggest that mural cells are essential for normal morphogenesis and patterning of the developing retinal vasculature.
BACKGROUND: The development of cerebral infarction is multifactorial, including both environmental and genetic factors. This study assessed the association between fibroblast growth factor (FGF)-related gene polymorphism...BACKGROUND: The development of cerebral infarction is multifactorial, including both environmental and genetic factors. This study assessed the association between fibroblast growth factor (FGF)-related gene polymorphisms and the incidence of cerebral infarction among patients on direct oral anticoagulants (DOACs). METHODS: Patients over 18 years old with atrial fibrillation who were receiving DOACs for cerebral infarction prevention at Ewha Womans University Mokdong Hospital and Ewha Womans University Seoul Hospital were enrolled in this analysis. Twenty-one single nucleotide polymorphisms (SNPs) from FGF1, FGF2, and FGFR1 were examined. In multivariable logistic regression analysis, three models (Model I: demographic factors only, Model II: demographic factors and genetic factors, and Model III: genetic factors and the CHADS-VASc score) were constructed to identify the risk factors related to cerebral infarction. RESULTS: Among the 536 candidate patients, 21 (3.9 %) experienced cerebral infarction while taking DOACs. From Model I and Model II, age ≥ 75 years and previous thromboembolic event history increased the risk of cerebral infarction. For genetic factors in Model II and III, FGF1 rs1596776 GG, FGFR1 rs6996321 AA, and FGFR1 rs7012413 TT genotypes were associated with a higher risk of cerebral infarction. The area under the receiver operating curve increased from 0.747 (Model I) to 0.822 (Model II) by adding genetic factors, demonstrating better model performance. CONCLUSIONS: This study uncovered the association between FGF-related gene polymorphisms and cerebral infarction among patients with atrial fibrillation undergoing DOAC therapy.
In recent years, the role of the cardiac microvasculature in modulating the symptoms and disease progression of patients affected by cardiac pathology has been reconsidered. The term cardiac microvascular disease (CMD) d...In recent years, the role of the cardiac microvasculature in modulating the symptoms and disease progression of patients affected by cardiac pathology has been reconsidered. The term cardiac microvascular disease (CMD) describes the set of functional and/or structural alterations of the cardiac microvasculature that reduce the ability of the heart to adequately increase its coronary blood flow to keep up with increased metabolic demand. CMD is involved in the evolution of heart disease of both ischemic and non-ischemic origin as well as in cardiac aging. The primary actors involved in this process are the cells of the stromal compartment, whose nature and biology are now investigated to a new level of detail thanks to single-cell omics studies. Recent studies on the genetics of extreme longevity have identified a polymorphic haplotype variant of the BPIFB4 gene that confers prolonged life span and health span, atheroprotective advantages, and an improved immune response. The aim of this review was to focus on the beneficial effects of the longevity-associated variant (LAV) of BPIFB4 on cardiac microvascular cell biology, providing novel and exciting mechanisms of its action directed against the development or progression of many age-related cardiovascular diseases, thus emphasizing its translational therapeutic potential.
BACKGROUND: Pulmonary hypertension (PH) is a serious vascular disease characterized by pulmonary vascular remodeling. Xuefu Zhuyu decoction (XFZYD) can potentially improve pulmonary vascular remodeling; however, its mech...BACKGROUND: Pulmonary hypertension (PH) is a serious vascular disease characterized by pulmonary vascular remodeling. Xuefu Zhuyu decoction (XFZYD) can potentially improve pulmonary vascular remodeling; however, its mechanism requires further investigation. METHODS: Rat models of monocrotaline (MCT)-induced PH and chronic thromboembolic pulmonary hypertension (CTEPH) were employed to investigate whether XFZYD has the potential to improve pulmonary vascular remodeling. After 21 days of XFZYD administration, the right ventricular systolic pressure (RVSP), organ indices, and wall thickness of pulmonary arteries of the rats were measured. Considering the possibility of endothelial-to-mesenchymal transition (EndMT), the specific mechanism of XFZYD in improving pulmonary vascular remodeling was further explored. Immunofluorescence, immunohistochemistry, and western blotting were used to detect the expression of EndMT markers, transforming growth factor-β1 (TGF-β1)/Smad pathway-related proteins, hypoxia-inducible factor-1α (HIF-1α), and levels of reactive oxygen species (ROS) in the lung tissues. RESULTS: XFZYD demonstrated significant efficacy in treating PH, as evidenced by its effects in both the rat models of MCT-induced PH and CTEPH. XFZYD remarkably improved pulmonary vascular remodeling while reducing RVSP and right ventricular hypertrophy. XFZYD has the potential to improve pulmonary vascular remodeling by inhibiting EndMT in the pulmonary vasculature. The underlying mechanism may be closely associated with the inhibition of TGF-β1/Smad and HIF-1α signaling pathways and the reduction of ROS levels in lung tissue by XFZYD. CONCLUSION: This study indicates that XFZYD may inhibit EndMT by modulating the ROS/HIF-1α/TGF-β1 signaling pathway, thereby improving pulmonary vascular remodeling. These findings provide a theoretical foundation for the clinical application of XFZYD in PH.
Osteonectin, a secreted glycoprotein, plays a role in muscle-wasting disease. However, its role in chronic heart failure (CHF) -induced systemic inflammation and postural control is unknown. Here we aim to assess the pot...Osteonectin, a secreted glycoprotein, plays a role in muscle-wasting disease. However, its role in chronic heart failure (CHF) -induced systemic inflammation and postural control is unknown. Here we aim to assess the potential association of soluble osteonectin with cardiac dysfunction and postural imbalance in CHF. The cardiac function, physical performance, including short physical performance battery (SPPB) for balance, handgrip strength (HGS), and the levels of plasma osteonectin and c-reactive protein (CRP) were assessed in controls (n = 56) and CHF patients (n = 286) presented with ischemic and non-ischemic CHF. CHF patients exhibited significantly lower HGS and postural balance accompanied by higher cardiac contractile dysfunction. Regardless of HF etiologies, the osteonectin and CRP levels were significantly higher in CHF patients vs. controls. The osteonectin exhibited a significant inverse correlation with left ventricular ejection fraction (LVEF) in both ischemic (r = 0.13, P < 0.0001) and non-ischemic (r = 0.18, P < 0.0001) CHF patients. Similarly, osteonectin has shown a strong negative correlation with cumulative SPPB score in both ischemic (r = 0.19, P < 0.0001) and non-ischemic (r = 0.22, P < 0.0001) patients. Further SPPB balance-based analysis demonstrated lower LVEF and markedly elevated osteonectin and CRP (P < 0.0001), particularly in patients with poor postural balance compared to those with relatively good balance. Importantly, osteonectin demonstrated significantly higher sensitivity and specificity for CHF diagnosis on ROC curve analysis. Taken together, higher osteonectin level is associated with LV dysfunction and postural imbalance irrespective of CHF etiologies. It may serve as a biomarker for physical disability and contractile dysfunction in CHF patients.
INTRODUCTION: Aspirin is commonly recommended for individuals who have experienced stroke or myocardial infarction (MI). Indobufen, a cyclooxygenase-1 inhibitor, has been studied as a potential alternative. We conducted...INTRODUCTION: Aspirin is commonly recommended for individuals who have experienced stroke or myocardial infarction (MI). Indobufen, a cyclooxygenase-1 inhibitor, has been studied as a potential alternative. We conducted a meta-analysis and trial sequential analysis (TSA) to compare indobufen with aspirin in patients requiring antiplatelet therapy. METHODS: We searched PubMed, Scopus, and Cochrane Central for studies that compared indobufen and aspirin antiplatelet therapies. We focused on efficacy outcomes, such as composite vascular events, MI, and ischemic stroke, and safety outcomes, such as major bleeding and any bleeding. Heterogeneity was assessed using I2 statistics, and our analysis followed the PRISMA guidelines. RESULTS: The review included 5 studies with 11,943 patients (indobufen n = 5952, 49.84 %), three involving post-MI and two involving post-stroke patients. No significant differences were found between the groups in composite vascular events at 90 days (RR 0.84; 95 % CI 0.46-1.53; p = 0.560; I2 = 53 %) and 1-year (RR 1.13; 95 % CI 0.99-1.29; p = 0.08; I2 = 0 %). MI (RR 0.73; 95 % CI 0.43-1.22; p = 0.22; I2 = 0 %), ischemic stroke (RR 1.16; 95 % CI 0.99-1.37; p = 0.06; I2 = 0 %), and cardiovascular death (RR 1.35; 95 % CI 0.80-2.26; p = 0.257; I2 = 0 %) at 1-year also showed no significant differences. Major bleeding at 1 year (RR 0.73; 95 % CI 0.41-1.31; p = 0.297; I2 = 64 %) was comparable, but any bleeding at 1 year showed a significant difference (RR 0.65; 95 % CI 0.43-0.98; p = 0.03; I2 = 87 %) favoring indobufen. Subgroup analysis of RCTs showed marginally significant increased risk regarding ischemic stroke with indobufen (RR 1.18; 95 % CI 1.00-1.39; p = 0.05). CONCLUSION: The efficacy and safety of antiplatelet therapy with indobufen were comparable to those of aspirin alone. Therefore, indobufen can be considered as a suitable alternative for patients who are intolerant or hypersensitive to aspirin. Nevertheless, additional trials involving larger populations are required to establish their clinical applicability.
Long non-coding RNA (lncRNA) may be involved in dysfunction of pulmonary artery endothelial cells (PAEC) and, thus, in pulmonary arterial hypertension (PAH) pathobiology. We screened the RNA expression profile of commerc...Long non-coding RNA (lncRNA) may be involved in dysfunction of pulmonary artery endothelial cells (PAEC) and, thus, in pulmonary arterial hypertension (PAH) pathobiology. We screened the RNA expression profile of commercial human PAEC (hPAEC) exposed to increased hydrostatic pressure, and found that the lncRNA Down syndrome critical region 9 (DSCR9) was the most regulated transcript (log2FC 1.89 vs control). We confirmed by RT-qPCR that DSCR9 levels were higher in PAEC isolated from patients with idiopathic PAH (iPAH-PAEC), as well as in induced pluripotent stem cell-derived endothelial cells (iPSC-EC) from a patient with BMPR2-mutated PAH, than in relevant controls. Moreover, a re-analysis of the publicly available GSE117261 microarray dataset revealed that DSCR9 was upregulated in the lung tissue of PAH patients. In silico simulation indicated that DSCR9 would be mainly located in the nucleus and could interact with calcium/calmodulin-dependent protein kinase II beta (CAMK2B) and nitric oxide synthase 3 (NOS3, encoding eNOS). CAMK2B levels resulted 3.4-fold higher (p < 0.05) in iPAH-PAEC transfected with a DSCR9-GFP carrying plasmid than with a GFP-only-carrying one. A trend for higher NOS3 expression was also noted. GFP immunostaining was predominantly nuclear and cytoplasmic upon DSCR9-GFP or GFP-only transfection, respectively. CAMK2B and NOS3 mRNA were also higher in iPAH-PAEC than control-PAEC in basal conditions. Instead, variations in total and phosphorylated CAMK2B, eNOS, and NO synthesis were inconsistent. We conclude that DSCR9 is upregulated in PAH-related endothelial cell models and influences CAMK2B and NOS3 expression. Future studies are necessary to determine whether DSCR9 affects NO availability, including in PAH.
The appropriate regulation of peripheral vascular tone is crucial for maintaining tissue perfusion. Myoendothelial junctions (MEJs), specialized connections between endothelial cells and vascular smooth muscle cells, are...The appropriate regulation of peripheral vascular tone is crucial for maintaining tissue perfusion. Myoendothelial junctions (MEJs), specialized connections between endothelial cells and vascular smooth muscle cells, are primarily located in peripheral resistance vessels. Therefore, these junctions, with their key membrane proteins, play a pivotal role in the physiological control of relaxation-contraction coupling in resistance arterioles, mainly mediated through endothelium-derived hyperpolarization (EDH). This review aims to illustrate the mechanisms involved in the initiation and propagation of EDH, emphasizing the role of membrane proteins involved in its generation (TRPV4, Piezo1, ASIC1a) and propagation (connexins, Notch). Finally, we discuss relevant studies on pathological events linked to EDH dysfunction and discuss novel approaches, including the effects of natural and dietary bioactive molecules, in modulating EDH-mediated vascular tone.
The risk for developing cardiovascular diseases dramatically increases in older individuals, and aging vasculature plays a crucial role in determining their morbidity and mortality. Aging disrupts endothelial balance bet...The risk for developing cardiovascular diseases dramatically increases in older individuals, and aging vasculature plays a crucial role in determining their morbidity and mortality. Aging disrupts endothelial balance between vasodilators and vasoconstrictors, impairing function and promoting pathological vascular remodeling. In this Review, we discuss the impact of key and emerging molecular pathways that transduce aberrant inflammatory signals (i.e., chronic low-grade inflammation-inflammaging), oxidative stress, and mitochondrial dysfunction in aging vascular compartment. We focus on the interplay between these events, which contribute to generating a vicious cycle driving the progressive alterations in vascular structure and function during cardiovascular aging. We also discuss the primary role of senescent endothelial cells and vascular smooth muscle cells, and the potential link between vascular and myeloid cells, in impairing plaque stability and promoting the progression of atherosclerosis. The aim of this summary is to provide potential novel insights into targeting these processes for therapeutic benefit.
Immune checkpoint therapy targeting the PD-1/PD-L1 axis has revolutionised the treatment of solid tumors. However, T cell exhaustion underpins resistance to current anti-PD-1 therapies, resulting in lower response rates...Immune checkpoint therapy targeting the PD-1/PD-L1 axis has revolutionised the treatment of solid tumors. However, T cell exhaustion underpins resistance to current anti-PD-1 therapies, resulting in lower response rates in cancer patients. CD28 is a T cell costimulatory receptor that can influence the PD-1 signalling pathway (and vice versa). CD28 signalling has the potential to counter T cell exhaustion by serving as a potential complementary response to traditional anti-PD-1 therapies. Here we discuss the interplay between PD-1 and CD28 in T cell immunotherapy and additionally how CD28 transcriptionally modulates T cell exhaustion. We also consider clinical attempts at targeting CD28; the challenges faced by past attempts and recent promising developments.
Aortic aneurysm is a common cardiovascular disease. Over time, the disease damages the structural and functional integrity of the aorta, causing it to abnormally expand and potentially rupture, which can be fatal. Sex di...Aortic aneurysm is a common cardiovascular disease. Over time, the disease damages the structural and functional integrity of the aorta, causing it to abnormally expand and potentially rupture, which can be fatal. Sex differences are evident in the disease, with men experiencing an earlier onset and higher incidence. However, women may face a worse prognosis and a higher risk of rupture. While there are some studies on the cellular and molecular mechanisms of aneurysm formation, it remains unclear how sex factors contribute to sexual dimorphism. Therefore, this review aims to summarize the role of sex in the occurrence of aortic aneurysms, offering valuable insights for disease prevention and the development of appropriate treatment options.
Angiogenesis plays a pivotal role in various pathological conditions, making it a key target in therapeutic development. Anti-angiogenic therapies are gaining traction for their potential in treating a range of angiogene...Angiogenesis plays a pivotal role in various pathological conditions, making it a key target in therapeutic development. Anti-angiogenic therapies are gaining traction for their potential in treating a range of angiogenesis-dependent diseases. Among these, endogenous angiogenesis inhibitors, particularly endostatin, have garnered significant attention for their therapeutic potential. While extensively studied for its anti-angiogenic effects in cancer, endostatin also exhibits anti-atherosclerotic and anti-fibrotic properties, broadening its therapeutic scope. Despite the successful clinical use of recombinant human endostatin in China for nearly two decades, its broader therapeutic potential remains underexplored. Thus, this review delves into the multifaceted applications of endostatin, examining its role in ocular diseases, inflammation, reproductive disorders, and tumor angiogenesis. Furthermore, it provides a comprehensive overview of its emerging roles beyond angiogenesis, particularly in the context of atherosclerosis and fibroproliferative conditions.
Ca signaling events are essential for maintaining cardiovascular health, regulating critical functions in both endothelial and cardiac cells. SARS-CoV-2 infection impinges this delicate balance, leading to severe cardiov...Ca signaling events are essential for maintaining cardiovascular health, regulating critical functions in both endothelial and cardiac cells. SARS-CoV-2 infection impinges this delicate balance, leading to severe cardiovascular complications. SARS-CoV-2 binds to the ACE2 receptor on endothelial and cardiomyocyte surfaces, triggering abnormal increases in intracellular Ca levels that promote endothelial dysfunction, inflammation, and hypercoagulation. In endothelial cells, this dysregulation activates a pro-inflammatory state and compromises vascular integrity. In cardiomyocytes, SARS-CoV-2-induced Ca imbalances contribute to arrhythmias and heart failure by promoting abnormal Ca cycling and energy metabolism disruptions. Additionally, the cytokine storm associated with COVID-19 amplifies these effects by further altering Ca handling, enhancing inflammatory responses, and promoting thrombosis. Targeting Ca channels, particularly endolysosomal two-pore channels, represents a promising therapeutic approach to counteract SARS-CoV-2's effects on Ca dynamics. Several FDA-approved drugs that modulate Ca signaling could be repurposed to prevent viral entry and mitigate cardiovascular damage. Understanding these Ca-related mechanisms offers valuable insights for developing treatments to reduce cardiovascular risk in COVID-19 and potentially future viral infections impacting the cardiovascular system.
Atherosclerosis is a multifaceted disease characterised by chronic inflammation and vascular remodelling, leading to plaque formation and cardiovascular complications. Recent evidence highlights the critical role of epsi...Atherosclerosis is a multifaceted disease characterised by chronic inflammation and vascular remodelling, leading to plaque formation and cardiovascular complications. Recent evidence highlights the critical role of epsins, a family of endocytic proteins, in the pathogenesis of atherosclerosis. This manuscript explores the multifarious functions of epsins in atherosclerosis, focusing on their involvement in angiogenesis, lymphangiogenesis, and the modulation of key signalling pathways. We discuss how epsins facilitate EndoMT through their interaction with the TGFβ signalling pathway, which contributes to vascular smooth muscle cell-like phenotypes and plaque instability. Additionally, we examine the therapeutic potential of targeting epsins, elucidating their interactions with crucial partners such as LDLR, LRP-1, and TLR 2/4, among others, in mediating lipid metabolism and inflammation. Furthermore, we highlight the promising prospects of epsin-targeting peptides and small interfering RNAs as therapeutic agents for atherosclerosis treatment. Despite these advancements, the research faces limitations, including a reliance on specific mouse models and a need for comprehensive studies on the long-term effects of epsin modulation. Therefore, future investigations should focus on elucidating the detailed mechanisms of epsin function and their implications in cardiovascular health, fostering collaborations to translate basic research into innovative therapeutic strategies. This work underscores the necessity for further exploration of epsins to unlock their full therapeutic potential in combating atherosclerosis and related cardiovascular diseases.
Kardassis D, Vindis C, Stancu CS
… +17 more, Toma L, Gafencu AV, Georgescu A, Alexandru-Moise N, Molica F, Kwak BR, Burlacu A, Hall IF, Butoi E, Magni P, Wu J, Novella S, Gamon LF, Davies MJ, Caporali A, de la Cuesta F, Mitić T
Despite the discovery and prevalent clinical use of potent lipid-lowering therapies, including statins and PCSK9 inhibitors, cardiovascular diseases (CVD) caused by atherosclerosis remain a large unmet clinical need, acc...Despite the discovery and prevalent clinical use of potent lipid-lowering therapies, including statins and PCSK9 inhibitors, cardiovascular diseases (CVD) caused by atherosclerosis remain a large unmet clinical need, accounting for frequent deaths worldwide. The pathogenesis of atherosclerosis is a complex process underlying the presence of modifiable and non-modifiable risk factors affecting several cell types including endothelial cells (ECs), monocytes/macrophages, smooth muscle cells (SMCs) and T cells. Heterogeneous composition of the plaque and its morphology could lead to rupture or erosion causing thrombosis, even a sudden death. To decipher this complexity, various cell model systems have been developed. With recent advances in systems biology approaches and single or multi-omics methods researchers can elucidate specific cell types, molecules and signalling pathways contributing to certain stages of disease progression. Compared with animals, in vitro models are economical, easily adjusted for high-throughput work, offering mechanistic insights. Hereby, we review the latest work performed employing the cellular models of atherosclerosis to generate a variety of omics data. We summarize their outputs and the impact they had in the field. Challenges in the translatability of the omics data obtained from the cell models will be discussed along with future perspectives.