Vascular Pharmacology

INTRODUCTION: Cancer needs perfusion for its growth and metastasis. Cancer cell-derived extracellular vesicles (CA-EVs) alter the tumor microenvironment (TME), potentially promoting angiogenesis. We hypothesize that conditions in the tumor, e.g., hypoxia, and in the target cells of the TME, e.g., nutrient deprivation or extracellular matrix, can affect the angiogenic potential of CA-EVs, which would contribute to explaining the regulation of tumor vascularization and its influence on cancer growth and metastasis...

Corticotropin releasing factor family peptides (CRF peptides) include 4 members, corticotropin releasing hormone (CRH), Urocortin (UCN1), UCN2 and UCN3. CRF peptides function via the two distinct receptors, CRF1 and CRF2 . Among them, CRH/CRF1 has been recognized to influence immunity/inflammation peripherally. Both pro- and anti-inflammatory effects of CRH are reported. Likewise, UCNs, peripherally in cardiovascular system have been documented to have both potent protective and harmful effects, with UCN1 acting on both CRF1 & CRF2 and UCN2 & UCN3 on CRF2 ...

The current approach to myocardial ischemia has been influenced by the misconception of a close link between ischemia and coronary atherosclerotic obstructions. Recent guidelines have, however, acknowledged the multifactorial nature of this condition, with an identifiable cause present in less than half of angina patients, and a large fraction with angina of unknown origin. Because of this background, focusing on cardiac energy metabolim offers new opportunities to manage myocardial ischemia even when its cause is unknown...

Treatment of ischemic cardiomyopathy has been the focus of increased attention by cardiologists due to recent evidence of an important outcome study comparing percutaneous coronary intervention (PCI) plus optimal medical treatment vs optimal medical treatment alone, concluding for the futility of myocardial revascularization by PCI. A relatively older trial of coronary artery bypass grafting (CABG) in the same condition, on the other hand, had concluded for some prognostic improvement at a long-term follow-up...

In patients with a suspected acute coronary syndrome, non-elevated (or uncertain) (NSTE-ACS) high sensitivity cardiac troponin, no ECG changes and no recurrence of chest pain, incorporating a coronary computed tomography angiogram (CCTA) or a non-invasive functional stress imaging test as part of the initial workup should be considered (Class IIA, Level of Evidence A). There are pros and cons with each diagnostic approach. CCTA imaging has high sensitivity for detecting coronary atherosclerosis but may not provide a diagnosis since most patients do not have obstructive coronary disease...

BACKGROUND: Hypertension is highly prevalent and remains one of the most frequent and preventable causes of cardiovascular morbidity and mortality. Yet, suboptimal blood pressure control is common. Hypertension clinics might play an important role in improving target attainment, by targeting drug therapy adherence, improving guideline compliance and by involving pharmacists. OBJECTIVES: We aimed to characterize patient drug therapy adherence, prescriber guideline compliance and pharmacist interventions at the hypertension clinic...

The notion that inflammation contributes to atherosclerosis has now gained considerable currency. Inflammation participates in atherosclerosis inception, progression, and thrombotic complications. Induced expression of endothelial leukocyte adhesion molecules and chemoattractant cytokines recruit blood cells to the arterial intima. Lesions can contain virtually every type of leukocyte. Monocytes mature into macrophages and imbibe lipids becoming foam cells, a hallmark of the atherosclerotic lesion. T lymphocytes can instruct the more numerous macrophages to express genes involved in the progression of the atheroma and its eventual destabilization...

CRISPR editing involves double-strand breaks in DNA with attending insertions/deletions (indels) that may result in embryonic lethality in mice. The prime editing (PE) platform uses a prime editing guide RNA (pegRNA) and a Cas9 nickase fused to a modified reverse transcriptase to precisely introduce nucleotide substitutions or small indels without the unintended editing associated with DNA double-strand breaks. Recently, engineered pegRNAs (epegRNAs), with a 3'-extension that shields the primer-binding site of the pegRNA from nucleolytic attack, demonstrated superior activity over conventional pegRNAs in cultured cells...

Adipsin is an adipokine predominantly synthesized in adipose tissues and released into circulation. It is also known as complement factor-D (CFD), acting as the rate-limiting factor in the alternative complement pathway and exerting essential functions on the activation of complement system. The deficiency of CFD in humans is a very rare condition. However, complement overactivation has been implicated in the etiology of numerous disorders, including cardiovascular disease (CVD). Increased circulating level of adipsin has been reported to promote vascular derangements, systemic inflammation, and endothelial dysfunction...

The long noncoding RNA (lncRNA) CARMN (cardiac mesoderm enhancer associated noncoding RNA) is a highly conserved lncRNA that expresses primarily by smooth muscle cells (SMCs). Recent literature demonstrates that CARMN plays a critical role in the differentiation and maintaining of the contractile state of vascular SMCs. Because aortic SMCs show diminished contractile proteins in abdominal aortic aneurysms (AAAs), we hypothesize that the expression of CARMN is downregulated in the aortic wall affected by aneurysm...

No abstract text is available yet for this article.

The prevalence of non-alcoholic fatty liver disease (NAFLD) and atherosclerosis remain high, which is primarily due to widespread adoption of a western diet and sedentary lifestyle. NAFLD, together with advanced forms of this disease such as non-alcoholic steatohepatitis (NASH) and cirrhosis, are closely associated with atherosclerotic-cardiovascular disease (ASCVD). In this review, we discussed the association between NAFLD and atherosclerosis and expounded on the common molecular biomarkers underpinning the pathogenesis of both NAFLD and atherosclerosis...

The optimal management of chronic coronary syndrome (CCS) patients has been a source of debate for several decades. Herein, we describe the evidence base comprising several landmark clinical trials including the most recent ISCHEMIA Trial, which, in aggregate, does not demonstrate a conclusive, incremental benefit of revascularization combined with optimal medical therapy (OMT) versus OMT alone in reducing prognostically-important clinical outcomes during long-term follow-up. For CCS patients with symptoms or quality of life not deemed refractory or unacceptable on medical therapy, a conservative approach to the judicious and selective use of revascularization plus OMT remains a justifiable evidence-based management strategy...

AIM: Endothelial dysfunction represents a key feature of the pathological process underlying micro and macro-vascular damage in Systemic Sclerosis (SSc). This study aims to improve knowledge of the physiopathology of vascular damage in SSc through the assessment of the endothelial dysfunction by Flow Mediated Dilation (FMD) and serum levels of circulating endothelial dysfunction markers and the correlation of macrovascular damage with clinical findings and microvascular capillaroscopic patterns...

BACKGROUND: Hypertension is a prevalent cardiovascular disease characterized by elevated blood pressure and increased vascular resistance. HDAC inhibitors have emerged as potential therapeutic agents due to their ability to modulate gene expression and cellular processes. YPX-C-05, a novel hydroxamic acid-based HDAC inhibitor, shows promise in its vasodilatory effects and potential targets for hypertension treatment. In this study, we aimed to elucidate the mechanisms underlying YPX-C-05's vasodilatory effects and explore its therapeutic potential in hypertension...

No abstract text is available yet for this article.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been at the forefront of health sciences research since its emergence in China in 2019 that quickly led to a global pandemic. As a result of this research, and the large numbers of infected patients globally, there were rapid enhancements made in our understanding of Coronavirus disease 2019 (COVID-19) pathology, including its role in the development of uncontrolled immune responses and its link to the development of endotheliitis and endothelial dysfunction...

BACKGROUND: Tirofiban is an antiplatelet treatment approved for acute coronary syndrome, but it has not been rigorously evaluated for efficacy and safety in patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT). METHODS: Electronic databases were systematically searched for studies conducted from January 1, 2015, to July 31, 2021, that evaluated tirofiban administration for patients with AIS treated with EVT in comparison with control...

The term "coronary microvascular dysfunction" (CMD) encompasses several pathogenetic mechanisms resulting in functional and/or structural changes in the coronary microcirculation. CMD often determines angina and myocardial ischemia in a broad spectrum of cardiovascular diseases, including patients with ischemia with non-obstructive coronary arteries or ischemia with obstructive coronary artery disease, infarction with non-obstructive coronary arteries, cardiomyopathies, the Takotsubo syndrome and heart failure, especially heart failure with preserved ejection fraction...

CTHRC1 is transiently expressed by activated fibroblasts during tissue repair and in certain cancers, and CTHRC1 derived from osteocytes is detectable in circulation. Because its biological activity is poorly understood, we investigated whether the N terminus of CTHRC1 encodes a propeptide requiring cleavage to become activated. The effects of full-length versus cleaved recombinant CTHRC1 on endothelial cell metabolism and gene expression were examined in vitro. Respirometry was performed on Cthrc1 null and wildtype mice to obtain evidence for biological activity of CTHRC1 in vivo...