Journal of Cardiovascular Pharmacology最新文献

Preeclampsia is a hypertensive disorder of pregnancy associated with substantial maternal morbidity and long-term cardiovascular risk, but the consistency of echocardiographic remodeling remains unclear. We conducted a mega-meta-analysis of left ventricular function and geometry, enabled by a large language model based suite of tools. A PROSPERO-registered review (CRD420251109103) searched PubMed, Scopus, and Embase without date limits. Synthesa AI screened more than 138,000 abstracts, extracted data, assessed risk of bias, and generated Bayesian analytic code, with all outputs validated by human reviewers. Seventy-five studies including met eligibility criteria. Preeclampsia was associated with a small but statistically significant reduction in ejection fraction (mean difference -0.87%, 95% CrI -1.58 to -0.16) and a clinically meaningful impairment in global longitudinal strain (-3.08%, 95% CrI -4.13 to -2.06). Left ventricular mass index was substantially higher in the preeclampsia group (+13.10 g/m 2 , 95% CrI 10.06 to 16.21), as was relative wall thickness (+0.062, 95% CrI 0.042 to 0.081), whereas fractional shortening showed no significant difference (-0.60%, 95% CrI -2.15 to +0.86). Moderator analyses revealed that BMI and parity significantly influenced strain, while gestational age at diagnosis accounted for nearly all variance in ventricular mass. This mega-meta-analysis defines a remodeling phenotype of preserved ejection fraction, impaired strain, and hypertrophic adaptation consistent with subclinical systolic dysfunction. Equally, it demonstrates the transformative role of LLM-based tools, showing that evidence syntheses of this magnitude can be automated, scaled, and standardized in ways previously unattainable.

Abstract: The global burden of mortality is largely attributable to cardiovascular diseases (CVDs), where altered metabolic homeostasis plays a critical role. The identification of lactylation as an epigenetic modification mediated by lactate has transformed the conventional view of this glycolysis byproduct from a mere metabolic intermediate to a multifaceted signaling molecule. This review comprehensively reveals the mechanistic insights underlying lactylation in CVDs, particularly in myocardial ischemia, atherosclerosis, and heart failure, highlighting its pivotal role in disease pathogenesis through modulation of transcriptional regulation, metabolic adaptation, and cellular differentiation. Considering the enzyme-regulated reversibility of lactylation, this work systematically evaluates its druggable targets, thereby establishing a conceptual foundation for combined metabolism-epigenetic therapeutics.

Abstract: Human-based technologies are revolutionizing cardiovascular pharmacology by offering innovative platforms that more accurately reflect human biology and disease mechanisms than traditional animal models. These approaches include tissue chips, microphysiologic systems, engineered heart tissues, cardiac organoids, and human cardiac slices-each contributing to substantial improvements in drug testing, mechanistic understanding, and translational relevance. Complementary advances in biobanking, omics technologies, and advanced imaging offer the opportunity for multidimensional characterization of cardiovascular phenotypes, while digital health tools and wearables expand our translational armamentarium with real-time physiologic monitoring and decentralized clinical trials. Artificial intelligence and machine learning further contribute discovery pipelines by facilitating data integration and predictive modeling. The application of clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR-Cas9) genome editing and in vitro to in vivo extrapolation frameworks underscores the growing precision and clinical orientation of these methodologies. Together, these innovations are reshaping basic research, drug development, regulatory science, and personalized medicine in cardiology. However, to fully realize their promise, challenges related to standardization, scalability, and ethical governance must be addressed. With strategic investment and cross-sector collaboration, human-based approaches are poised to lead the next generation of cardiovascular research-delivering safer, more effective therapies tailored to human-specific biology.

Abstract: Vascular calcification (VC) is prevalent in patients with chronic kidney disease and raises the risk of cardiovascular death. The study aimed to evaluate the protective effects of rosuvastatin and/or vitamin K on VC in a rat model of adenine-induced chronic kidney disease and to explore the potential underlying mechanisms. Forty Wistar albino rats were divided equally into 5 groups: rats of group I (control group) received drug vehicle, rats of group II received an adenine-containing diet, rats of group III received an adenine-containing diet + oral rosuvastatin (5 mg/kg/day), rats of group ΙV received an adenine-containing diet + oral vitamin K (40 mg/kg/day), and rats of group V received adenine-containing diet and combined treatment of rousvastatin and vitamin K. The entire experiment lasted for 5 weeks. Then, aortas and kidneys were collected for biochemical and histopathologic analysis. Oxidative stress and inflammation markers were measured in kidney and aortic homogenates, whereas alkaline phosphatase activity, osteocalcin, and bone morphogenic protein-2 levels and autophagic markers were measured in aortic homogenates. Treatment with rosuvastatin and/or vitamin K improved renal function and decreased aortic calcium accumulation. In addition, they decreased alkaline phosphatase activity and osteogenic markers level while increasing the expression of autophagic markers. The beneficial effects of rosuvastatin and/or vitamin K are further supported by histopathologic examination of aortas and kidneys. The combined treatment produced the best outcomes in all studied parameters. The study concluded that rosuvastatin and/or vitamin K could improve VC by combating oxidative stress, decreasing inflammation, and autophagy upregulation.

Abstract: Hypertension remains the leading cause of morbidity and mortality worldwide and requires more understanding of its molecular basis. This study investigated cellular stress responses and senescence signaling in vascular and renal tissues of deoxycorticosterone-acetate-salt hypertensive rats and the effect of resveratrol and exercise on these processes. Biochemical measurements in plasma and molecular (using Western Blot and Quantitative Real-Time-polymerase chain reaction methods) and histopathologic (Hematoxylin-Eosin and Masson's Trichrome staining) examinations in the kidney and aorta were performed. The increase in kidney weight, kidney/body weight ratio, plasma blood urea nitrogen, and creatinine levels of hypertensive animals was improved by exercise and resveratrol. Both interventions reduced GRP78/p-PERK-mediated endoplasmic reticulum stress and restored mitophagy via PINK1-SIRT3 in hypertensive renal and vascular tissues. Decreased vascular enos mRNA expression in hypertensive rats was enhanced by resveratrol treatment. The expression of NLRP3 inflammasome-related molecules and nf-ĸb in both tissues was increased in hypertensive animals. The positive effect of both treatments on inflammatory parameters was more pronounced in the kidney than in the aorta. The increased cellular senescence-related molecules p53 and il-6 were reversed by exercise and resveratrol in both tissues of hypertensive rats. Hypertension caused more obvious structural and inflammatory histopathologic changes in renal tissue than in vascular tissue. Regular exercise ameliorated these hypertension-induced renal alterations more than resveratrol. This study revealed that hypertension induces cellular stress responses including endoplasmic reticulum stress, impaired mitophagy, inflammation, and consequently senescence, leading to structural alterations in a tissue-dependent manner. Regular exercise and resveratrol have different positive regulatory effects on these renal and vascular impairments caused by hypertension.

Abstract: Cardiovascular diseases are life-threatening conditions with multifactorial causes. As the most abundant cells in the vascular wall, vascular smooth muscle cells (VSMCs) play a crucial role in regulating vascular tone. Under physiologic conditions, VSMCs predominantly demonstrate a contractile phenotype. However, this phenotype can be altered in response to microenvironmental stimuli, particularly during injury or pathologic conditions. We performed a systematic literature review to examine the phenotypic switching of VSMCs from a contractile state to a dedifferentiated state, and the role of senescence in VSMC dysfunction. Special attention was given to the impact of microenvironmental stress on VSMCs transdifferentiation into multiple phenotypes, including macrophage-like cells, foam cells, and mesenchymal stem cells. Prolonged or excessive phenotypic switching of VSMCs leads to cellular senescence, characterized by decreased proliferative capacity, increased secretion of inflammatory factors (senescence-associated secretory phenotype), and a tendency toward calcification. Senescent VSMCs undergo transdifferentiation into multiple phenotypes, which promote arterial calcification and fibrosis, thereby exacerbating cardiovascular disease progression. Emerging evidence reveals that VSMC phenotypic switching and senescence share common molecular pathways, offering new opportunities for developing dual-target therapies against age-related cardiovascular diseases by simultaneously modulating cellular plasticity and aging processes.

Abstract: Pulmonary arterial hypertension is a progressive cardiovascular disease characterized by elevated pulmonary arterial pressure and vascular remodeling. However, the underlying mechanisms remain unclear. This study reveals a novel mechanism by which oxidative stress reduced glutathione peroxidase 4 (GPX4) expression in both rat and human pulmonary arterial smooth muscle cells (PASMCs), establishing a reciprocal regulatory relationship between GPX4 and reactive oxygen species. GPX4 deficiency in PASMCs exacerbated inflammation, evidenced by increased IL-6 and TNF-α, and promoted extracellular matrix remodeling, indicated by elevated fibronectin and collagen II. Moreover, GPX4 inhibition disrupted mitochondrial function by downregulating key mitochondrial regulators peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α) and mitochondrial transcription factor A. Simultaneously, it promoted glycolysis, leading to increased lactate production through the upregulation of lactate dehydrogenase A and hexokinase 2. These effects were associated with the long noncoding RNA TUG1, which appeared to modulate GPX4 stability. Collectively, our findings identify GPX4 as a critical regulator of inflammation, extracellular matrix remodeling, and metabolic homeostasis in PASMCs, providing new insights into the molecular mechanisms underlying pulmonary arterial hypertension and identify potential therapeutic targets.

Abstract: Although selective SGLT2 inhibitors improve heart failure (HF) outcomes, they do not consistently reduce atherothrombotic events (myocardial infarctions and strokes). Clinical trials with sotagliflozin, the first dual SGLT1/2 inhibitor, have shown significant reductions in both HF outcomes and atherothrombotic events: an effect not seen with highly selective SGLT2 inhibitors such as empagliflozin. This effect may be related to SGLT1 inhibition, because SGLT1 is widely expressed in the myocardium, platelets, and endothelial cells, suggesting a potential antithrombotic mechanism. The SOTA-THROMBOSIS trial is a randomized, cross-over study in healthy volunteers (n = 16) comparing the antithrombotic effects of dual SGLT1/2 inhibition with sotagliflozin and selective SGLT2 inhibition with empagliflozin. All participants will receive each treatment for 4 weeks, separated by a 1-month washout. Blood thrombogenicity under high and low shear rate conditions will be assessed using the Badimon perfusion chamber. Additional assessments include platelet aggregation (Multiplate Analyzer) and clot formation kinetics using thromboelastometry (RoTEM). Measurements will be performed at baseline (pretreatment) and at the end of each treatment period. The cross-over design-where each participant receives both study treatments and serves as his/her own control-significantly reduces both, intrasubject and intragroup variability. We hypothesize that both treatments will reduce blood thrombogenicity compared with baseline, with sotagliflozin offering a more marked antithrombotic effect than empagliflozin. This trial will provide novel mechanistic insights into the antithrombotic activity of SGLT1/2 inhibition. If confirmed, these findings may explain the additional cardiovascular protection observed with sotagliflozin and support its use in patients with HF at high thrombotic risk.