Finally, Progress in Pulmonary Hypertension Associated with Heart Failure with Preserved Ejection Fraction.
Finally, Progress in Pulmonary Hypertension Associated with Heart Failure with Preserved Ejection Fraction.
复制标题
最后，与射血分数保留的心力衰竭相关的肺动脉高压的进展。
DOI：
10.1165/rcmb.2017-0035ed
复制
发表时间：
2017
影响因子：
6.4
通讯作者：
Kaminski,Naftali
中科院分区：
文献类型：
--
作者：
Fares,WassimH;Kaminski,Naftali
The complexity, nonlinearity, adaptability, and compartmentalization of the biological systems have led biologists in recent years to expand on the results of molecular biology, using high-throughput approaches, complex computational methods, and systems biology approaches. In the field of pulmonary hypertension (PH), we have seen significant progress in dissecting the molecular mechanisms, mostly after gene discoveries in patients with familial PH and careful hypothesis-driven investigations in animal models of the disease. However, with the expanded understanding of PH in humans and the refined World Health Organization (WHO) classification of PH, recognition of the limitations of traditional animal models has increased, leading to greater efforts to molecularly characterize human samples and to search for novel models that better mimic the human subphenotypes of PH. In this issue of the Journal, two articles, by Kelly and colleagues (pp. 488–496) and Meng and colleagues (pp. 497–505), tackle PH associated with heart failure with preserved ejection fraction (PH-HFpEF), an increasingly important syndrome commonly accompanied by other features of the metabolic syndrome (1–3). Despite its prevalence and the fact that it is an important cause of mortality and morbidity, PH-HFpEF has so far lacked a specific therapy, an animal model, and a central molecular hypothesis connecting the systemic features with the development of PH. In the two articles in this issue of the Journal (1, 2), the authors use an elegant approach of screening susceptibility among various strains of inbred mice to develop a novel mouse model of PH-HFpEF and to identify a potential novel molecular regulator mechanism underlying this syndrome. Both investigations are based on the results of an initial exposure of 36 different mice strains to 20 weeks of a high-fat diet and studying their susceptibility to PH.In the first article, Meng and colleagues (2) identify the AKR/J strain as a strain that developed the combination of cardiovascular changes, PH, and right and left ventricular hypertrophy, and attributes of the metabolic syndrome including obesity, glucose intolerance, insulin resistance, and hyperlipidemia. Using detailed cardiovascular phenotyping methods, they suggest convincingly that this is a novel model for a PH-HFpEF mouse model, which in many ways is comparable to human WHO group 2 PH. They also demonstrate a therapeutic response (decreased pulmonary artery pressures) after ongoing supplementation of nitrite and metformin. In the second article, Kelly and colleagues (1) apply network analysis to mouse genome-wide association study results to identify human-relevant PH genes. They identify single nucleotide polymorphisms that associate with elevated right ventricular systolic pressures in mice and then filter them on the basis of their
影响因子：
7.7
作者：
Florez-Vargas, Oscar;Brass, Andy;Nenadic, Goran
通讯作者：
Nenadic, Goran