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Patients with stable coronary disease were randomly assigned to an initial invasive strategy with angiography and revascularization if appropriate or to medical therapy alone. At 3.2 years, there was no significant difference between the groups with respect to the estimated rate of ischemic events. The findings were sensitive to the definition of myocardial infarction.

At a median of 2.2 years, patients with stable coronary artery disease and advanced kidney disease who were treated with an invasive strategy of coronary angiography with revascularization if indicated did not have a lower risk of death or MI than those who were treated with a conservative strategy of medical therapy alone.

In a randomized trial involving patients with a low LVEF and viable myocardium who received optimal medical therapy, PCI did not lead to a lower incidence of death or hospitalization for heart failure.

Energy stress, such as ischemia, induces mitochondrial damage and death in the heart. Degradation of damaged mitochondria by mitophagy is essential for the maintenance of healthy mitochondria and survival. Here, we show that mitophagy during myocardial ischemia was mediated predominantly through autophagy characterized by Rab9-associated autophagosomes, rather than the well-characterized form of autophagy that is dependent on the autophagy-related 7 (Atg) conjugation system and LC3. This form of mitophagy played an essential role in protecting the heart against ischemia and was mediated by a protein complex consisting of unc-51 like kinase 1 (Ulk1), Rab9, receptor-interacting serine/thronine protein kinase 1 (Rip1), and dynamin-related protein 1 (Drp1). This complex allowed the recruitment of trans-Golgi membranes associated with Rab9 to damaged mitochondria through S179 phosphorylation of Rab9 by Ulk1 and S616 phosphorylation of Drp1 by Rip1. Knockin of Rab9 (S179A) abolished mitophagy and exacerbated the injury in response to myocardial ischemia, without affecting conventional autophagy. Mitophagy mediated through the Ulk1/Rab9/Rip1/Drp1 pathway protected the heart against ischemia by maintaining healthy mitochondria.

Circular RNAs are generated from many protein-coding genes, but their role in cardiovascular health and disease states remains unknown. Here we report identification of circRNA transcripts that are differentially expressed in post myocardial infarction (MI) mouse hearts including circFndc3b which is significantly down-regulated in the post-MI hearts. Notably, the human circFndc3b ortholog is also significantly down-regulated in cardiac tissues of ischemic cardiomyopathy patients. Overexpression of circFndc3b in cardiac endothelial cells increases vascular endothelial growth factor-A expression and enhances their angiogenic activity and reduces cardiomyocytes and endothelial cell apoptosis. Adeno-associated virus 9 -mediated cardiac overexpression of circFndc3b in post-MI hearts reduces cardiomyocyte apoptosis, enhances neovascularization and improves left ventricular functions. Mechanistically, circFndc3b interacts with the RNA binding protein Fused in Sarcoma to regulate VEGF expression and signaling. These findings highlight a physiological role for circRNAs in cardiac repair and indicate that modulation of circFndc3b expression may represent a potential strategy to promote cardiac function and remodeling after MI. Circular RNAs (circRNAs) are non-coding RNAs generated from pre-mRNAs of coding genes by the splicing machinery whose function in the heart is poorly understood. Here the authors show that AAV-mediated delivery of the circRNA circFndc3b prevents cardiomyocyte apoptosis, enhances angiogenesis, and attenuates LV dysfunction post-MI in mice by regulating FUS-VEGF-A signalling.

Sequencing of the gene encoding apolipoprotein C3 ( APOC3 ) in participants in two general-population studies identified three rare loss-of-function mutations associated with low plasma triglyceride levels. The risk of ischemic vascular disease was reduced by 41% among carriers of these mutations. Low-density lipoprotein (LDL) cholesterol is the principal target of lipid drugs that have been developed for the prevention of cardiovascular disease. However, even among patients with substantial reductions in LDL cholesterol levels, residual cardiovascular risk persists. 1 Spurred by the strong association between high levels of both fasting and nonfasting triglycerides and the risk of cardiovascular disease, 2 – 6 recent genetic studies involving mendelian randomization have suggested that high levels of nonfasting triglycerides are causally associated with an increased risk of ischemic cardiovascular disease, independent of high-density lipoprotein (HDL) cholesterol levels. 7 , 8 Plasma triglycerides are markers of so-called remnant particles, which include . . .

Ischemic injury represents the most frequent cause of death and disability, and it remains unclear why, of all body organs, the brain is most sensitive to hypoxia. In many tissues, type 4 NADPH oxidase is induced upon ischemia or hypoxia, converting oxygen to reactive oxygen species. Here, we show in mouse models of ischemia in the heart, brain, and hindlimb that only in the brain does NADPH oxidase 4 (NOX4) lead to ischemic damage. We explain this distinct cellular distribution pattern through cell-specific knockouts. Endothelial NOX4 breaks down the BBB, while neuronal NOX4 leads to neuronal autotoxicity. Vascular smooth muscle NOX4, the common denominator of ischemia within all ischemic organs, played no apparent role. The direct neuroprotective potential of pharmacological NOX4 inhibition was confirmed in an ex vivo model, free of vascular and BBB components. Our results demonstrate that the heightened sensitivity of the brain to ischemic damage is due to an organ-specific role of NOX4 in blood–brain-barrier endothelial cells and neurons. This mechanism is conserved in at least two rodents and humans, making NOX4 a prime target for a first-in-class mechanism-based, cytoprotective therapy in the unmet high medical need indication of ischemic stroke.

Among patients with ischemic cardiomyopathy, coronary-artery bypass grafting added to medical therapy led to significantly lower rates of death from any cause and of cardiovascular death over 10 years than did medical therapy alone. Advances in the management of cardiovascular risk factors and acute coronary syndromes have increased survival among patients with coronary artery disease, transforming it into a chronic disease that affects 15.5 million U.S. patients; however, coronary artery disease still accounts for more than 538,000 deaths yearly in the United States alone. 1 The major long-term manifestations of coronary artery disease, left ventricular dysfunction, and heart failure are projected to affect 8 million patients by 2030, which has enormous societal implications. 1 Landmark clinical trials have established coronary-artery bypass grafting (CABG) as an effective treatment for patients with disabling angina symptoms. 2 – 4 In these . . .

Patients with ischemic heart disease and advanced kidney disease were randomly assigned to an invasive or a conservative strategy. As reported separately, the invasive strategy did not reduce clinical events. In this analysis of health-status outcomes, there were no benefits with the invasive strategy.

The role of myocardial viability assessment in identifying patients with ischemic cardiomyopathy who will benefit from surgical revascularization is controversial. This study assessed myocardial viability and its relationship to long-term outcomes in 601 patients with ischemic cardiomyopathy who were assigned to surgical revascularization plus medical therapy or medical therapy alone.