Extracellular Vesicles in Comorbidities Associated with Ischaemic Heart Disease: Focus on Sex, an Overlooked Factor

Abstract

Extracellular vesicles (EV) are emerging early markers of myocardial damage and key mediators of cardioprotection. Therefore, EV are becoming fascinating tools to prevent cardiovascular disease and feasible weapons to limit ischaemia/reperfusion injury. It is well known that metabolic syndrome negatively affects vascular and endothelial function, thus creating predisposition to ischemic diseases. Additionally, sex is known to significantly impact myocardial injury and cardioprotection. Therefore, actions able to reduce risk factors related to comorbidities in ischaemic diseases are required to prevent maladaptive ventricular remodelling, preserve cardiac function, and prevent the onset of heart failure. This implies that early diagnosis and personalised medicine, also related to sex differences, are mandatory for primary or secondary prevention. Here, we report the contribution of EV as biomarkers and/or therapeutic tools in comorbidities predisposing to cardiac ischaemic disease. Whenever possible, attention is dedicated to data linking EV to sex differences.

Protective Role of Platelets in Myocardial Infarction and Ischemia/Reperfusion Injury

“…Level of PMVs and endothelial MVs was elevated in obese woman compared with women of similar age with normal weight [117]. Increased level of PMVs was associated with excessive adipose tissue and metabolic state of adipocytes and platelets [115,119]. Improvement in PMV levels has been reported in obese patients 12 months after gastrectomy or by caloric restriction and exercise [119,120].…”

“…EVs carry bioactive molecules, such as proteins, lipids, amino acids, mRNAs, and miRNAs. EVs cargo depends on many factors, including changes in the microenvironment such as oxygen content, inflammation, age, and gender [101,115]. Going forward, risk factors and comorbidities associated with ischemic diseases, such as age, gender, and metabolic diseases, are linked with changes in circulating EVs; therefore, EVs can be useful biomarkers [116].…”

“…Exercise-derived EVs protection was related with activation of ERK1/2 and heat shock protein 27 (HSP27) signaling in cardiac IRI. erefore, exercise-derived EVs may serve as potent therapy against cardiac IRI [115,118]. Platelet EVs formed during heavy exercises stimulated human endothelial cells by enhancing angiogenesis and proliferation in vitro [122].…”

“…Penna et al suggested that sex-dependent hormonal modulations may affect changes in EVs in pathological conditions. erefore, in the context of EV as new biomarkers of ischemia/reperfusion and comorbidities, further research needs to paid more attention to gender influence [115].…”

Extracellular vesicles (EVs) in ischemic conditioning and angiogenesis: Focus on endothelial derived EVs

“…Along with microenvironmental cues, sex [47] and comorbidities, such as metabolic syndrome (MS), dictates EV features mainly impacting on their cargo. Given the role played by diabetes in hampering cardioprotection and angiogenesis, here we focus on type 1 and 2 diabetes mellitus (T1DM and T2DM, respectively) [48].…”