MicroRNAs are small non-coding post-translational biomolecules which, when expressed, modify their target genes. It is estimated that microRNAs regulate production of approximately 60% of all human proteins and enzymes that are responsible for major physiological processes. In cardiovascular disease pathophysiology, there are several cells that produce microRNAs, including endothelial cells, vascular smooth muscle cells, macrophages, platelets, and cardiomyocytes. There is a constant crosstalk between microRNAs derived from various cell sources. Atherosclerosis initiation and progression are driven by many pro-inflammatory and pro-thrombotic microRNAs. Atherosclerotic plaque rupture is the leading cause of cardiovascular death resulting from acute coronary syndrome (ACS) and leads to cardiac remodeling and fibrosis following ACS. MicroRNAs are powerful modulators of plaque progression and transformation into a vulnerable state, which can eventually lead to plaque rupture. There is a growing body of evidence which demonstrates that following ACS, microRNAs might inhibit fibroblast proliferation and scarring, as well as harmful apoptosis of cardiomyocytes, and stimulate fibroblast reprogramming into induced cardiac progenitor cells. In this review, we focus on the role of cardiomyocyte-derived and cardiac fibroblast-derived microRNAs that are involved in the regulation of genes associated with cardiomyocyte and fibroblast function and in atherosclerosis-related cardiac ischemia. Understanding their mechanisms may lead to the development of microRNA cocktails that can potentially be used in regenerative cardiology.

Ischemic event in one arterial territory increases the risk of a subsequent ischemic event. Circulating microRNAs (miRs) emerge as a potential clinical tool to assess risk of subsequent atherothrombotic events such as cardiovascular death (CVD), myocardial infarction (MI) and ischemic stroke (IS). In this prospective study, we searched for athero-specific miRs related to cardiovascular event risk in patients with symptomatic coronary, carotid lesion, or both territories involvements. The choice of particular miRs was based on database research (Pub-Med, Bethesda, MD, USA) taking into consideration the relationship with development of atherosclerosis and potential prognostic value. Levels of circulating miRs (miR-1-3p, miR-16-5p, miR-34a-5p, mir-122-5p, miR-124-3p, miR-133a-3p, miR-133b, miR-134-5p, miR-208b-3p, miR-375 and miR-499-5p) were compared in 142 patients with an acute ischemic event resulting from carotid and/or coronary artery stenosis, who underwent revascularization for symptomatic lesion. A 6-year prospective evaluation of CVD/MI/IS risk was performed. Patients with two-territory as compared to single-territory involvement differed in levels of miR-1-3p (p = 0.016), miR-16-5p (p < 0.001), miR-34a-5p (p = 0.018), miR-122-5p (p = 0.007), miR-124-3p (p < 0.001) and miR-499-5p (p < 0.001). During follow-up, 62 (43.7%) episodes of CVD/MI/IS occurred. In multivariate Cox analysis, miR-122-5p (HR = 1.0006, 95%CI = 1.0001–1.0011) and peripheral artery disease (PAD) (HR = 2.16, 95%CI = 1.26–3.70) were associated with CVD/MI/IS risk; miR-1-3p (HR = 2.73, 95%CI = 1.22–6.12) and PAD (HR = 3.47, 95%CI = 1.88–6.41) with CVD; miR-122-5p (HR = 1.0001, 95%CI = 1.000–1.0002) and creatinine level (HR = 1.02, 95%CI = 1.01–1.04) with IS, and miR-16-5p (HR = 1.0004, 95%CI = 1.0001–1.0008) with MI. Expression of miR-1-3p, miR-16-5p and miR-122-5p during incident ischemia may be possible risk factors of secondary cardiovascular event(s).

Ischemic stroke (IS) related to atherosclerosis of large arteries is one of the leading causes of mortality and disability in developed countries. Atherosclerotic internal carotid artery stenosis (ICAS) contributes to 20% of all cerebral ischemia cases. Nowadays, atherosclerosis prevention and treatment measures aim at controlling the atherosclerosis risk factors, or at the interventional (surgical or endovascular) management of mature occlusive lesions. There is a definite lack of the established circulating biomarkers which, once modulated, could prevent development of atherosclerosis, and consequently prevent the carotid-artery-related IS. Recent studies emphasize that microRNA (miRNA) are the emerging particles that could potentially play a pivotal role in this approach. There are some research studies on the association between the expression of small non-coding microRNAs with a carotid plaque development and vulnerability. However, the data remain inconsistent. In addition, all major studies on carotid atherosclerotic plaque were conducted on cell culture or animal models; very few were conducted on humans, whereas the accumulating evidence demonstrates that it cannot be automatically extrapolated to processes in humans. Therefore, this paper aims to review the current knowledge on how miRNA participate in the process of carotid plaque formation and rupture, as well as stroke occurrence. We discuss potential target miRNA that could be used as a prognostic or therapeutic tool.

MicroRNAs (miRs) are promising diagnostic, prognostic and therapeutic biomolecules for atherosclerotic cardiovascular disease. Atherosclerotic occlusive disease concerns a large population of patients, carrying the highest incidence of fatal and non-fatal adverse events, such as myocardial infarction, ischemic stroke, and limb ischemia, worldwide. Consistently, miRs are involved in regulation and pathogenesis of atherosclerotic coronary artery disease (CAD), acute coronary syndromes (ACS), both with ST-segment (STEMI) and non-ST segment elevation myocardial infarctions (NSTEMI), as well as cardiac remodeling and fibrosis following ACS. However, the genetic and molecular mechanisms underlying adverse outcomes in CAD are multifactorial, and sometimes difficult to interpret for clinicians. Therefore, in the present review paper we have focused on the clinical meaning and the interpretation of various miRs findings, and their potential application in routine clinical practice.

Introduction Circulating microRNAs (miRNAs) levels are potentially important biomarkers and therapeutic targets of cerebral ischemic event (CIE) in patients with internal carotid artery stenosis (ICAS). Aim This prospective study investigated associations between circulating miRNAs and...

Non-atherosclerotic aortic arch pathologies (NA-AAPs) and anatomical variants are characterized as rare cardiovascular diseases with a low incidence rate, below 1 case per 2000 population, but enormous heterogeneity in terms of anatomical variants, i.e., Takayasu disease (TAK) and fibromuscular dysplasia (FMD). In specific clinical scenarios, NA-AAPs constitute life-threatening disorders. Methods: In this study, 82 (1.07%) consecutive patients with NA-AAPs (including 38 TAKs, 26 FMDs, and 18 other AAPs) out of 7645 patients who underwent endovascular treatment (EVT) for the aortic arch and its side-branch diseases at a single institution between 2002 and 2022 were retrospectively reviewed. The recorded demographic, biochemical, diagnostic, operative, and postoperative factors were reviewed, and the functional outcomes were determined during follow-up. A systematic review of the literature was also performed. Results: The study group comprised 65 (79.3%) female and 17 (21.7%) male subjects with a mean age of 46.1 ± 14.9 years. Overall, 62 (75.6%) patients were diagnosed with either cerebral ischemia symptoms or aortic arch dissection on admission. The EVT was feasible in 59 (72%) patients, whereas 23 (28%) patients were referred for medical treatment. In EVT patients, severe periprocedural complications occurred in two (3.39%) patients, including one periprocedural death and one cerebral hyperperfusion syndrome. During a median follow-up period of 64 months, cardiovascular events occurred in 24 (29.6%) patients (5 deaths, 13 ISs, and 6 myocardial infarctions). Repeated EVT for the index lesion was performed in 21/59 (35.6%) patients, including 19/33 (57.6%) in TAK and 2/13 (15.4%) in FMD. In the AAP group, one patient required additional stent-graft implantation for progressing dissection to the iliac arteries at 12 months. A baseline white blood count (odds ratio [HR]: 1.25, 95% confidence interval [CI]: 1.11–1.39; p < 0.001) was the only independent prognostic factor for recurrent stenosis, while a baseline hemoglobin level (HR: 0.73, 95%CI: 0.59–0.89; p = 0.002) and coronary involvement (HR: 4.11, 95%CI: 1.74–9.71; p = 0.001) were independently associated with a risk of major cardiac and cerebral events according to the multivariate Cox proportional hazards regression analysis. Conclusions: This study showed that AAPs should not be neglected in clinical settings, as it can be a life-threatening condition requiring a multidisciplinary approach. The knowledge of prognostic risk factors for adverse outcomes may improve surveillance in this group of patients.