Pulmonary Arterial Hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a progressive disorder in which endothelial dysfunction and vascular remodeling obstruct small pulmonary arteries, resulting in increased pulmonary vascular resistance and pulmonary pressures. This leads to reduced cardiac output, right heart failure, and ultimately death. In this review, we attempt to answer some important questions commonly asked by patients diagnosed with PAH pertaining to the disease, and aim to provide an explanation in terms of classification, diagnosis, pathophysiology, genetic etiologies, demographics, and prognostic factors. Furthermore, important molecular pathways that are central to the pathogenesis of PAH are reviewed, including nitric oxide, prostacyclin, endothelin-1, reactive oxygen species, and endothelial and smooth muscle proliferation.

Endothelial and Smooth Muscle Cell Interactions in the Pathobiology of Pulmonary Hypertension

“…A dysfunctional EDNOsGC-cGMP-PKG signaling pathway constitutes one of the most fundamental and initial changes in the development of PH (1,33), resulting from aberrant expression of eNOS (34), reduced NO production caused by eNOS uncoupling (35)(36)(37)(38), diminished NO bioavailability caused by oxidative stress (39,40), diminished activities of sGC (41,42) and PKG (26,(43)(44)(45)(46), and augmented activity of phosphodiesterase type 5 (47).…”

“…It acts in co-ordination with other vasodilators and antiproliferative agents and is also counteracted by agents with vasoconstrictor and mitogenic activities. The balance of these opposing effects maintains the homeostasis of pulmonary circulation (1,60). This is exemplified by the interaction between NO and ET-1.…”

“…Oxidative stress is present in PH (49,86,87), and ET-1 increases ROS production in PASMCs (88). Because NO signaling is compromised by oxidative stress, the increased ROS production evoked by ET-1 may promote vasoconstriction and vascular remodeling via the suppression of NO activity (1,60). A study with fetal ovine pulmonary ECs cocultured with PASMCs showed that the eNOS promoter activity and protein levels in ECs were suppressed by SMC-derived hydrogen peroxide production stimulated by ET-1, suggesting that a feedback mechanism exists that may contribute to the already impaired NO signaling (88) (Figure 1).…”

“…These mechanisms operate in a complicated but co-ordinated manner to maintain the homeostasis of the pulmonary circulation. Under pathological conditions, the interaction between ECs and VSMCs may be chronically altered so that a sustained increase in vasocontractility and abnormal vascular proliferation develops, which leads to high pulmonary artery pressure, vascular remodeling, right ventricular hypertrophy, and the clinical condition, pulmonary hypertension (PH) (1,(21)(22)(23)(24). This article discusses the recent progress in our knowledge of the interactions between ECs and SMCs through paracrine mechanisms, MEJs, and EVs in the pathobiology of PH.…”

Cardiovascular Magnetic Resonance Imaging in the Evaluation of the Right Ventricle and its Pathologies

“…29 O método clássico para diagnóstico de HP é o cateterismo em coração direito apresentando pressão média de artéria pulmonar > 25 mmHg e pressão de oclusão de artéria pulmonar < 15 mmHg. 30 O aumento progressivo da pressão pulmonar e a resistência vascular pulmonar resultam em sobrecarga de VD, com hipertrofia, dilatação e consequente disfunção dessa câmara. 30,31 A RMC fornece informações importantes sobre alterações na função e morfologia ventricular direita, como aumento da espessura de sua parede e movimento paradoxal do septo interventricular, além de dilatação de artérias pulmonares, características importantes no diagnóstico da HP primária, assim como para descartar outras doenças que possam levar a alterações nessa cavidade.…”