Circulation research
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Pulmonary arterial hypertension (PAH) is a progressive and fatal disease for which there is an ever-expanding body of genetic and related pathophysiological information on disease pathogenesis. Many germline gene mutations have now been described, including mutations in the gene coding bone morphogenic protein receptor type 2 (BMPR2) and related genes. Recent advanced gene-sequencing methods have facilitated the discovery of additional genes with mutations among those with and those without familial forms of PAH (CAV1, KCNK3, EIF2AK4). ⋯ These multi-faceted variations are an active area of investigation in the field, including but not limited to common genetic variants and epigenetic processes, and may provide novel opportunities for pharmacological intervention in the near future. They also highlight the need for a systems-oriented multi-level approach to incorporate the multitude of biological variations now associated with PAH. Ultimately, an in-depth understanding of the genetic factors relevant to PAH provides the opportunity for improved patient and family counseling about this devastating disease.
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The appropriate timing of angiography to facilitate revascularization is essential to optimize outcomes in patents with ST-segment-elevation myocardial infarction and non-ST-segment-elevation acute coronary syndromes. Timely reperfusion of the infarct-related coronary artery in ST-segment-elevation myocardial infarction both with fibrinolysis or percutaneous coronary intervention minimizes myocardial damage, reduces infarct size, and decreases morbidity and mortality. Primary percutaneous coronary intervention is the preferred reperfusion method if it can be performed in a timely manner. ⋯ However, despite reductions in door-to-balloon times, there has been little change during the past several years in in-hospital mortality, suggesting additional factors including patient-related delays, optimization of tissue-level perfusion, and cardioprotection must be addressed to improve patient outcomes further. Early angiography followed by revascularization when appropriate also reduces rates of death, MI, and recurrent ischemia in patients with non-ST-segment-elevation acute coronary syndromes, with the greatest benefits realized in the highest risk patients. Among patients with non-ST-segment-elevation acute coronary syndromes with multivessel disease, choice of revascularization modality should be made as in stable coronary artery disease, with a goal of complete ischemic revascularization.
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Circulation research · May 2014
Humans with atherosclerosis have impaired ABCA1 cholesterol efflux and enhanced high-density lipoprotein oxidation by myeloperoxidase.
The efflux capacity of high-density lipoprotein (HDL) with cultured macrophages associates strongly and negatively with coronary artery disease status, indicating that impaired sterol efflux capacity might be a marker-and perhaps mediator-of atherosclerotic burden. However, the mechanisms that contribute to impaired sterol efflux capacity remain poorly understood. ⋯ Our observations indicate that myeloperoxidase may contribute to the generation of dysfunctional HDL with impaired ABCA1 efflux capacity in humans with atherosclerosis. Quantification of chlorotyrosine and oxidized methionine in circulating HDL might be useful indicators of the risk of cardiovascular disease that are independent of HDL-cholesterol.