Current Vascular Pharmacology - Volume 21, Issue 5, 2023

Peripheral artery disease (PAD), defined as lower extremity arterial disease, constitutes an underestimated aspect of the menopause-associated risk of atherosclerotic cardiovascular disease (ASCVD). Accumulation of ASCVD risk factors, such as atherogenic dyslipidaemia, diabetes, and arterial hypertension, after the transition to menopause may contribute to atherosclerotic plaque formation in peripheral arteries. However, inconsistency exists among studies as to whether transition to menopause increases the risk of PAD, although early menopause (<45 years) or premature ovarian insufficiency may accelerate peripheral atherosclerotic plaque formation. Menopausal hormone therapy may decrease the risk of PAD if administered early (i.e., within the first 5-6 years after last menstruation), whereas it has no effect in women with established ASCVD.

Testosterone levels in men begin declining in the early years of adulthood, with a 1-2% reduction/year. Low testosterone levels in men are associated with obesity, metabolic syndrome, diabetes mellitus, dyslipidaemia, hypertension and increased cardiovascular mortality. However, observational studies of testosterone levels in males and their relationship with peripheral arterial disease (PAD) have yielded mixed results; only some cohorts show a clear association with low free testosterone levels. This discrepancy may, in part, be due to methodological issues with estimating free testosterone but also to different effects of testosterone on the vessel wall and metabolism. While testosterone improves glycaemic control, has anti-obesity effects and induces vasodilation, it also stimulates platelet aggregation and increases the haematocrit. Androgen deprivation treatment for advanced prostate cancer may be associated with elevated cardiovascular risk, as is testosterone abuse for performance enhancement. On the other hand, judicious treatment of male hypogonadism or testosterone treatment of trans-men appears to be safe.

Background: A list of drugs that can induce takotsubo cardiomyopathy (TCM) was published in 2011 and 2016. The aim of the present review was to update this list.Methods: Similar to the 2011 and 2016 reviews, from April 2015 to May 2022 case reports of druginduced TCM were identified by a comprehensive search in Medline/PubMed database. The search terms were: takotsubo cardiomyopathy, tako-tsubo cardiomyopathy, stress cardiomyopathy, transientleft- ventricular ballooning syndrome, apical ballooning syndrome, ampulla cardiomyopathy OR broken heart syndrome; together with 128;œiatrogenic128;, 128;œinduced by128; OR 128;œdrug-induced128;. Registers published in English or Spanish, in humans, and with full texts were retrieved. Articles that recognized any drug associated with the development of TCM were selected.Results: Overall, 184 manuscripts were identified by the search. A total of 39 articles were included after an exhaustive revision. Eighteen drugs as possible triggers of TCM were identified in the current update. Of them, 3 (16.7%) have been previously identified, and 15 (83.3%) are different from the previous reports. Thus, the list of drugs as possible triggers of TCM updated in 2022 includes 72 drugs.Conclusion: There are new case reports that link drugs with the development of TCM. The current list is principally made up of drugs that generate sympathetic overstimulation. However, some of the listed drugs do not have a clear link with sympathetic activation.

Objective: To investigate the current status and development trend of research on exosomes in cardiovascular disease (CVD) using bibliometric analysis and to elucidate trending research topics.Methods: Research articles on exosomes in CVD published up to April 2022 were retrieved from the Web of Science database. Data were organized using Microsoft Office Excel 2019. CiteSpace 6.1 and VOSviewer 1.6.18 were used for bibliometric analysis and result visualization.Results: Overall, 256 original research publications containing 190 fundamental research publications and 66 clinical research publications were included. "Extracellular vesicle" was the most frequent research keyword, followed by "microrna," "apoptosis," and "angiogenesis." Most publications were from China (187, 73.05%), followed by the United States (57, 22.27%), the United Kingdom (7, 2.73%), and Japan (7, 2.73%). A systematic review of the publications revealed that myocardial infarction and stroke were the most popular topics and that exosomes and their contents, such as microRNAs (miRNAs), play positive roles in neuroprotection, inhibition of autophagy and apoptosis, promotion of angiogenesis, and protection of cardiomyocytes.Conclusion: Research on exosomes in CVD has attracted considerable attention, with China having the most published studies. Fundamental research has focused on CVD pathogenesis; exosomes regulate the progression of CVD through biological processes, such as the inflammatory response, autophagy, and apoptosis. Clinical research has focused on biomarkers for CVD; studies on using miRNAs in exosomes as disease markers for diagnosis could become a future trend.

Background: Selenium (Se) is an essential trace element that is involved in several pathophysiological functions. The relationship of Se with cardiovascular disease remains inconclusive, especially regarding the role of different selenospecies.Objective: The present study assessed the levels of Se distribution in plasma selenoproteins, namely glutathione peroxidase 3 (GPx3), selenoprotein P (SelP) and selenoalbumin (SeAlb) and total Se in selenoproteins in relation to 10-year cardiovascular risk in the ATTICA prospective study.Methods: A sub-sample from the ATTICA Study's database, consisting of 278 subjects (114 women and 164 men) with data on Se and selenoproteins levels, was considered. SeGPx3, SelP, and SeAlb in human plasma were simultaneously determined by high-performance liquid chromatography (HPLC) coupled with inductively coupled plasma mass spectrometry (ICP-MS) at baseline. The duration of the follow-up was 8.74 ±2.36 years (mean± standard deviation) and cardiovascular outcomes were recorded. Cox proportional hazards models were applied with total Se or selenoprotein Se as independent variables adjusted for several covariates.Results: Total Se in selenoproteins was positively related to 10-year relative risk of cardiovascular disease (Hazard Ratios of 3rd vs 2nd tertile 10.02, 95% CI:1.15, 92.34). Subjects with high Se but low SeGPx3, as identified by discordant percentiles in the distribution of SeGPx3 and Se, had a higher cardiovascular risk.Conclusion: The differentiated effects of circulating selenoproteins on cardiovascular disease risk in the present study, suggest the importance of redox regulation by specific selenoproteins.

Aim: This study aims to explore the impact of the synthetic cannabinoid methyl 2-(1-(4- fluorobenzyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (MDMB-FUBINACA) on the angiogenesis process in human brain microvascular endothelial cells.Background: Synthetic cannabinoids (SCs) are substances that mimic the natural components found in the cannabis plant. SCs are considered prohibited substances that have a clear impact on the central nervous system (CNS).Objectives: The purpose of this study is to explore how MDMB-FUBINACA influences angiogenesis in human brain microvascular endothelial cells and to clarify the pathways related to the cannabinoid receptors.Methods: Human brain microvascular endothelial cells (hBMECs) were grown in the medium containing Dulbecco Modified Eagle Medium (DMEM/F12) using an endothelial cell growth kit. Endothelial cell viability was evaluated using the MTT test. Migration ability was measured using the Wound healing test. The angiogenic capability was measured using a Tube Formation assay. Real-time polymerase chain reaction (RT-PCR) was utilized to explore the mRNA concentrations following MDMBFUBINACA treatment. ELISA and Western blotting were also employed to measure the protein levels.Results: MDMB-FUBINACA greatly increases tube formation, endothelial cell proliferation, and migration. Pro-angiogenic factors such as angiopoietins 1 and 2 (ANG-1 and 2) and vascular endothelial growth factor (VEGF) were shown to be increased at both the RNA and protein levels.Conclusion: MDMB-FUBINACA induces the progression of the angiogenesis process by inducing the expression of pro-angiogenic factors. These findings aim toward developing novel treatments for angiogenesis- related disorders.