Role of Redox Homeostasis and Inflammation in the Pathogenesis of Pulmonary Arterial Hypertension

Abstract

This review addresses pulmonary arterial hypertension (PAH), an incurable disease, which determines high morbidity and mortality. Definition of the disease, its characteristics, classification, and epidemiology are discussed. A difficulty in the diagnosis of PAH due to the lack of symptoms specificity is highlighted. Echocardiographic analysis and electrocardiogram of patients help in the diagnosis and in the follow up of the disease. Nevertheless, right ventricle (RV) catheterization constitutes the gold standard for diagnosing PAH. Oxidative stress and inflammation, in an interactive manner, play a major role in the development of pulmonary vascular remodeling and consequent increase of pulmonary pressure. The latter results in an increase in RV afterload, culminating with RV hypertrophy, which may progress to failure. Both clinical and experimental studies have shown increased oxidative stress and inflammation, not only in lungs and pulmonary vasculature but also in RV. The use of experimental models, such as the monocrotaline-induced PAH, has helped in the understanding of the pathophysiology of PAH, as well as in the development of new therapeutic strategies. In addition to the traditional therapeutics, the use of therapeutic interventions capable of modulating oxidative stress and inflammation may offer newer strategies in the prevention as well as management of this disease.

Alginate Oligosaccharide Alleviates Monocrotaline-Induced Pulmonary Hypertension via Anti-Oxidant and Anti-Inflammation Pathways in Rats

“…26,27) Aside from the adverse effects of ROS, the upregulation of vascular NADPH oxidase evoked proliferation and apoptosis-resistance of the pulmonary arterial wall cells. 2) In this study, our data showed that the MDA level and NADPH oxidase expression were significantly increased in MCT-induced pulmonary hypertension rats, and AOS reduced the MCT-induced MDA production and NADPH oxidase expression. These results indicated that AOS protected pulmonary hypertension rats via the regulation of redox states.…”

“…1) Current available therapies for PAH are limited, mostly either designed to depress vascular contractility or reduce pulmonary arterial resistance, such as calcium channels inhibitors, phosphodiesterase-5 inhibitors, prostacyclin analogues, soluble guanylate cyclase agonists, and inhaled nitric oxide. 2) However, these drugs fail to reverse the progression of PAH and improve the poor prognosis. Thus, more effective pharmacological interventions are urgently needed for the treatment of PAH.…”

“…Specifically, MCT initiates endothelial damage and triggers obstructive vascular remodeling with the presence of oxidative stress and inflammatory response. 2) In this study, we used the MCT-induced pulmonary hypertension rat model to investigate whether AOS could prevent pulmonary hypertension and pulmonary vascular remodeling. The potential mechanisms underlying the protective effects were also explored.…”

Oxidative Stress and Its Implications in the Right Ventricular Remodeling Secondary to Pulmonary Hypertension

“…Oxidative stress plays a key role in pulmonary vascular remodeling, which in turn increases the RV after-load leading to RV hypertrophy and eventual RV failure (Bello-Klein et al, 2018). Additionally, it has been shown that the RV is more vulnerable to oxidative stress than the LV (Reddy and Bernstein, 2015), potentially because the RV cannot upregulate manganese superoxide dismutase expression, an enzyme that combats ROS (Shults et al, 2018).…”

The relationship between Plasma Markers and Essential Hypertension in Middle-aged and Elderly Chinese Population: A Community Based Cross-sectional Study

“…Earlier studies have recognized the role of inflammatory pathways activation as an important pathological event in the development of hypertension 3 . This growing evidence suggests that systemic inflammation endorses endothelial damage, which further contributes to physiological alterations in the endothelium 4 .…”