Rationale:: MicroRNAs are small RNAs that control gene expression. Besides their cell intrinsic function, recent studies reported that microRNAs are released by cultured cells and can be detected in the blood. Objective:: To address the regulation of circulating microRNAs in patients with stable coronary artery disease. Methods and Results:: To determine the regulation of microRNAs, we performed a microRNA profile using RNA isolated from n=8 healthy volunteers and n=8 patients with stable coronary artery disease that received state-of-the-art pharmacological treatment. Interestingly, most of the highly expressed microRNAs that were lower in the blood of patients with coronary artery disease are known to be expressed in endothelial cells (eg, miR-126 and members of the miR-17∼92 cluster). To prospectively confirm these data, we detected selected microRNAs in plasma of 36 patients with coronary artery disease and 17 healthy volunteers by quantitative PCR. Consistent with the data obtained by the profile, circulating levels of miR-126, miR-17, miR-92a, and the inflammation-associated miR-155 were significantly reduced in patients with coronary artery disease compared with healthy controls. Likewise, the smooth muscle–enriched miR-145 was significantly reduced. In contrast, cardiac muscle–enriched microRNAs (miR-133a, miR-208a) tend to be higher in patients with coronary artery disease. These results were validated in a second cohort of 31 patients with documented coronary artery disease and 14 controls. Conclusions:: Circulating levels of vascular and inflammation-associated microRNAs are significantly downregulated in patients with coronary artery disease.

Aims: To evaluate the impact of the COVID-19 pandemic on patient admissions to Italian cardiac care units (CCUs). Methods and Results: We conducted a multicentre, observational, nationwide survey to collect data on admissions for acute myocardial infarction (AMI) at Italian CCUs throughout a 1 week period during the COVID-19 outbreak, compared with the equivalent week in 2019. We observed a 48.4% reduction in admissions for AMI compared with the equivalent week in 2019 (P < 0.001). The reduction was significant for both ST-segment elevation myocardial infarction [STEMI; 26.5%, 95% confidence interval (CI) 21.7–32.3; P = 0.009] and non-STEMI (NSTEMI; 65.1%, 95% CI 60.3–70.3; P < 0.001). Among STEMIs, the reduction was higher for women (41.2%; P = 0.011) than men (17.8%; P = 0.191). A similar reduction in AMI admissions was registered in North Italy (52.1%), Central Italy (59.3%), and South Italy (52.1%). The STEMI case fatality rate during the pandemic was substantially increased compared with 2019 [risk ratio (RR) = 3.3, 95% CI 1.7–6.6; P < 0.001]. A parallel increase in complications was also registered (RR = 1.8, 95% CI 1.1–2.8; P = 0.009). Conclusion: Admissions for AMI were significantly reduced during the COVID-19 pandemic across Italy, with a parallel increase in fatality and complication rates. This constitutes a serious social issue, demanding attention by the scientific and healthcare communities and public regulatory agencies.

Type 2 diabetes mellitus (DM) is a common metabolic disorder predisposing to diabetic cardiomyopathy and atherosclerotic cardiovascular disease (CVD), which could lead to heart failure through a variety of mechanisms, including myocardial infarction and chronic pressure overload. Pathogenetic mechanisms, mainly linked to hyperglycemia and chronic sustained hyperinsulinemia, include changes in metabolic profiles, intracellular signaling pathways, energy production, redox status, increased susceptibility to ischemia, and extracellular matrix remodeling. The close relationship between type 2 DM and CVD has led to the common soil hypothesis, postulating that both conditions share common genetic and environmental factors influencing this association. However, although the common risk factors of both CVD and type 2 DM, such as obesity, insulin resistance, dyslipidemia, inflammation, and thrombophilia, can be identified in the majority of affected patients, less is known about how these factors influence both conditions, so that efforts are still needed for a more comprehensive understanding of this relationship. The genetic, epigenetic, and environmental backgrounds of both type 2 DM and CVD have been more recently studied and updated. However, the underlying pathogenetic mechanisms have seldom been investigated within the broader shared background, but rather studied in the specific context of type 2 DM or CVD, separately. As the precise pathophysiological links between type 2 DM and CVD are not entirely understood and many aspects still require elucidation, an integrated description of the genetic, epigenetic, and environmental influences involved in the concomitant development of both diseases is of paramount importance to shed new light on the interlinks between type 2 DM and CVD. This review addresses the current knowledge of overlapping genetic and epigenetic aspects in type 2 DM and CVD, including microRNAs and long non-coding RNAs, whose abnormal regulation has been implicated in both disease conditions, either etiologically or as cause for their progression. Understanding the links between these disorders may help to drive future research toward an integrated pathophysiological approach and to provide future directions in the field.

Background—: Circulating levels of microRNA (miR) have been proposed as biomarkers for cardiovascular disease. To identify the heart as a potential source for miRs released into the circulation, we measured concentration gradients across the coronary circulation for muscle-enriched (miR-133a, miR-499, miR-208a), vascular (miR-126, miR-92a), leukocyte-related (miR-155), and platelet-enriched (miR-223) miRs. Methods and Results—: Circulating miRs were measured by TaqMan polymerase chain reaction in EDTA-plasma simultaneously obtained from the aorta and the coronary venous sinus in patients without coronary artery disease (n=7), with stable coronary artery disease (n=31), and with troponin-positive acute coronary syndromes (n=19). Circulating levels of the muscle-enriched miR-499 (>20-fold; P <0.01), miR-133a (11-fold; P <0.01), and miR-208a (5-fold; P <0.01) were significantly elevated in the aorta of troponin-positive acute coronary syndrome patients compared with patients with coronary artery disease. Importantly, there was a significant increase in circulating levels of miR-499 and miR-133a across the coronary circulation in troponin-positive acute coronary syndrome patients, suggestive of a release into the coronary circulation during myocardial injury. Indeed, miR-499 concentration gradients were significantly correlated with the extent of myocardial damage as measured by high-sensitivity troponin T ( r =0.70, P <0.01). In contrast, circulating levels of miR-126 ( P =0.16) decreased during transcoronary passage in patients with evidence of myocardial injury, suggesting consumption during transcoronary passage. Conclusions—: Muscle-enriched miR-499 and miR-133a are released from the heart into the coronary circulation on myocardial injury, whereas the vascular miR-126 is consumed during transcoronary passage. The differential regulation of circulating miRs during the transcoronary passage might provide important insights to exploit their role as cardiac biomarkers. Clinical Trial Registration—: URL: http://www.germanctr.de . Unique identifier: DRKS00000207; in German Clinical Trials Registry.

Stroke is the second-most common cause of death worldwide. The pathophysiology of ischemic stroke (IS) is related to inflammation, atherosclerosis, blood coagulation, and platelet activation. MicroRNAs (miRNAs) play important roles in physiological and pathological processes of neurodegenerative diseases and progression of certain neurological diseases, such as IS. Several different miRNAs, and their target genes, are recognized to be involved in the pathophysiology of IS. The capacity of miRNAs to simultaneously regulate several target genes underlies their unique value as diagnostic and prognostic markers in IS. In this review, we focus on the role of miRNAs as diagnostic and prognostic biomarkers in IS. We discuss the most common and reliable detection methods available and promising tests currently under development. We also present original results from bioinformatic analyses of published results, identifying the ten most significant genes (HMGB1, YWHAZ, PIK3R1, STAT3, MAPK1, CBX5, CAPZB, THBS1, TNFRSF10B, RCOR1) associated with inflammation, blood coagulation, and platelet activation and targeted by miRNAs in IS. Additionally, we created miRNA-gene target interaction networks based on Gene Ontology (GO) information derived from publicly available databases. Among our most interesting findings, miR-19a-3p is the most widely modulated miRNA across all selected ontologies and might be proposed as novel biomarker in IS to be tested in future studies.