Vascular pharmacology最新文献

The interaction between metabolic reprogramming and key signaling pathways is required for vascular smooth muscle cells (VSMCs) phenotypic transitions and the development of disease. In response to pathological stimuli, VSMCs experience metabolic reprogramming to meet their increased energy demands and biomass synthesis. Metabolite-derived post translational modifications (PTMs) act as a key player in linking metabolic reprogramming to the VSMC phenotypic transitions. The alteration of metabolites of glucose, lipids and amino acids in the microenvironment also governs key signaling pathways via PTMs in VSMCs. Here, we introduce the basic processes of metabolite-derived PTMs, including phosphorylation, succinylation, acetylation, lactylation, O-GlcNAcylation, palmitoylation, crotonylation, methylation, serotonylation and glutamylation, emphasize the importance of cross talk of PTMs and summarize the underlying mechanisms of metabolite-derived PTMs in regulating the VSMC phenotypic transitions.

Aims: We examined the association between ticagrelor pretreatment and angiographic no-reflow in ST-segment elevation myocardial infarction (STEMI), with in-hospital mortality as a secondary outcome and clinical phenotyping as an exploratory objective.

Methods: In a retrospective multicentre registry (2018-2021), 623 patients referred for percutaneous coronary intervention were compared by loading strategy: pretreatment at first medical contact or deferred before PCI. Cohort-wide inverse probability of treatment weighting (IPTW), using a clinical covariate-balancing propensity model and 50 imputations, estimated adjusted risk ratios (RRs). Outcome-blind latent class analysis preceded a treatment-weighted comparison of class-specific no-reflow risks.

Results: No-reflow occurred in 28/464 pretreated patients versus 27/159 comparators (6.0% versus 17.0%); the crude RR was 0.36 (95% CI 0.22-0.58), and the IPTW-adjusted RR was 0.43 (95% CI 0.24-0.74; P = 0.003). Ten patients died (adjusted RR 0.46, 95% CI 0.13-1.67). Three classes comprised 328, 231 and 64 patients, but their pretreatment-standardised no-reflow risks did not establish prognostic separation.

Conclusions: Ticagrelor pretreatment was associated with lower angiographic no-reflow after propensity weighting. The adjusted mortality and exploratory class-risk findings did not reach statistical significance. Residual confounding and uncertain covariate timing limit causal interpretation, and prospective validation is required.

Population aging is changing the needs of patients seen in cardio-oncology. Older adults with cancer often have cardiovascular disease, multimorbidity, and reduced physiological reserve, which can complicate treatment and recovery. Patients of the same chronological age may differ considerably in cardiovascular health, functional capacity, and treatment tolerance. Frailty and geriatric assessment can help characterize these differences and inform care. This review examines the biological mechanisms linking aging, cancer, and cardiovascular disease and discusses their implications for cardiovascular risk assessment, cancer treatment decisions, and long-term survivorship. Treatment decisions require consideration of the expected oncological benefit, cardiovascular risk, physiological reserve, life expectancy, and patient preferences. Identifying and addressing reversible vulnerabilities may help patients tolerate effective anticancer therapy while preserving function and quality of life. During survivorship, cardiovascular care should account for previous treatment exposure, changing health status, and adherence to preventive therapies. Closer collaboration between cardio-oncology and geriatric medicine may improve the assessment and management of older patients. Evidence specific to frail and very old adults remains limited. Prospective studies are needed to determine whether geriatric and biological aging measures improve cardiovascular risk prediction, treatment decisions, and patient outcomes.

Vascular smooth muscle cells (VSMCs) exhibit a remarkable phenotypic spectrum in response to injury, inflammation, metabolic stress, and aging through state changes encoded in chromatin. This review examines how DNA methylation and hydroxymethylation, histone modifiers, chromatin readers, adenosine triphosphate (ATP)-dependent chromatin remodelers, three-dimensional genome organization, and non-coding RNAs (ncRNAs) shape VSMC plasticity in intimal hyperplasia, atherosclerosis and vascular aging. Bromodomain-containing protein 4 (BRD4) is used as a case study because it links acetyl-lysine recognition to transcriptional programs and BRD4 inhibition has been reported to affect VSMC biology in vivo. Based on published evidence, we discuss the timing and delivery of potential vascular epigenetic targeting: short-term, local chromatin-directed therapy may help restrain maladaptive VSMC proliferation after acute artery injury, whereas chronic conditions, including atherosclerosis and vascular aging, would require careful long-term dosing that preserves endothelial repair, VSMC contractile state and hematopoietic safety. These therapeutic implications remain preclinical hypotheses, with clinical efficacy remaining to be established.

Introduction: Optic atrophy 1 (OPA1) is a mitochondrial inner-membrane GTPase that coordinates mitochondrial fusion, cristae organization, and respiratory efficiency. Beyond mitochondrial bioenergetics, OPA1 contributes to cardiovascular homeostasis, including the maintenance of vascular cell function and phenotype. Although increasing OPA1 expression has been proposed to improve mitochondrial performance, the consequences of sustained OPA1-driven oxidative activation in the lipid-exposed cardiovascular system remain incompletely defined. Here, we investigated cardiac structure, tissue metabolism, and cardiomyocyte bioenergetics in mice with systemic OPA1 overexpression maintained on a high-fat diet (HFD).

Methods: OPA1-overexpressing mice were fed high-fat diet for 20 weeks, followed by indirect calorimetry and echocardiographic analysis. Tissues were used for OMICs investigation and metabolic analysis.

Results: OPA1-overexpressing mice displayed preserved global left-ventricular systolic function and ventricular volumes but presented reduced anterior and lateral wall thickness. Histological analysis further revealed a decrease in cardiomyocyte cross-sectional area accompanied by increased myocardial collagen deposition. Cardiac triglyceride content was elevated, whereas cholesterol content was unchanged. In neonatal cardiomyocytes, OPA1 overexpression resulted in increased oxygen consumption, with the strongest response observed in cells co-incubated with very-low-density lipoprotein. Under this lipid-rich condition, ATP-linked respiration, maximal respiration, and spare respiratory capacity were increased.

Discussion: Collectively, these findings indicate that systemic OPA1 overexpression was associated with myocardial lipid accumulation and early fibrotic remodeling during HFD feeding, despite preserved systolic function. In vitro, OPA1 overexpression increased cardiomyocyte respiratory capacity under lipid-rich conditions. These data identify a context-dependent effect of OPA1 in which enhanced respiratory capacity may become maladaptive when lipid supply exceeds coordinated oxidative and storage capacity.