Molecular mechanisms of right ventricular dysfunction in pulmonary arterial hypertension: focus on the coronary vasculature, sex hormones, and glucose/lipid metabolism

被引:33
作者
Agrawal, Vineet [1 ]
Lahm, Tim [2 ]
Hansmann, Georg [3 ]
Hemnes, Anna R. [4 ]
机构
[1] Vanderbilt Univ, Med Ctr, Dept Med, Div Cardiol, 2220 Pierce Ave,383 Preston Res Bldg, Nashville, TN 37232 USA
[2] Indiana Univ, Dept Med, Indianapolis, IN USA
[3] Hannover Med Sch, Dept Pediat Cardiol & Crit Care, Hannover, Germany
[4] Vanderbilt Univ, Dept Med, Med Ctr, Div Allergy Pulmonol & Crit Care, Nashville, TN USA
关键词
Pulmonary arterial hypertension (PAH); right ventricular failure (RV failure); sex hormones; metabolism; coronary vasculature; RIGHT HEART-FAILURE; FATTY-ACID UPTAKE; THERAPEUTIC TARGET; MITOCHONDRIAL DYSFUNCTION; NATRIURETIC PEPTIDE; CARDIAC-HYPERTROPHY; INSULIN-RESISTANCE; EJECTION FRACTION; GENE-EXPRESSION; EMERGING ROLE;
D O I
10.21037/cdt-20-404
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Pulmonary arterial hypertension (PAH) is a rare, life-threatening condition characterized by dysregulated metabolism, pulmonary vascular remodeling, and loss of pulmonary vascular cross-sectional area due to a variety of etiologies. Right ventricular (RV) dysfunction in PAH is a critical mediator of both long-term morbidity and mortality. While combinatory oral pharmacotherapy and/or intravenous prostacyclin aimed at decreasing pulmonary vascular resistance (PVR) have improved clinical outcomes, there are currently no treatments that directly address RV failure in PAH. This is, in part, due to the incomplete understanding of the pathogenesis of RV dysfunction in PAH. The purpose of this review is to discuss the current understanding of key molecular mechanisms that cause, contribute and/or sustain RV dysfunction, with a special focus on pathways that either have led to or have the potential to lead to clinical therapeutic intervention. Specifically, this review discusses the mechanisms by which vessel loss and dysfunctional angiogenesis, sex hormones, and metabolic derangements in PAH directly contribute to RV dysfunction. Finally, this review discusses limitations and future areas of investigation that may lead to novel understanding and therapeutic interventions for RV dysfunction in PAH.
引用
收藏
页码:1522 / 1540
页数:19
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