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Therapeutic Targeting of Mineralocorticoid Receptors in Pulmonary Hypertension: Insights from Basic Research
Abstract: Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling and associated with adverse outcomes. In patients with PH, plasma aldosterone levels are elevated, suggesting that aldosterone and its receptor, the mineralocorticoid receptor (MR), play an important role in the pathophysiology of PH. The MR plays a crucial role in adverse cardiac remodeling in left heart failure. A series of experimental studies from the past few years indicate that MR activation promotes adverse cellular processes that lead to pulmonary vascular remodeling, including endothelial cell apoptosis, smooth muscle cell (SMC) proliferation, pulmonary vascular fibrosis, and inflammation. Accordingly, in vivo studies have demonstrated that pharmacological inhibition or cell-specific deletion of the MR can prevent disease progression and partially reverse established PH phenotypes. In this review, we summarize recent advances in MR signaling in pulmonary vascular remodeling based on preclinical research and discuss the potential, but also the challenges, in bringing MR antagonists (MRAs) into clinical application
Physiological and Pathological Responses to Hypoxia and High Altitude
The appearance of photosynthetic organisms about 3 billion years ago increased the partial pressure of oxygen (PO2) in the atmosphere and enabled the evolution of organisms that use glucose and oxygen to produce ATP by oxidative phosphorylation. Hypoxia is commonly defined as the reduced availability of oxygen in the tissues produced by different causes, which include reduction of atmospheric PO2 as in high altitude, and secondary to pathological conditions such as sleep breathing and pulmonary disorders, anemia, and cardiovascular alterations leading to inadequate transport, delivery, and exchange of oxygen between capillaries and cells. Nowadays, it has been shown that hypoxia plays an imp...
Molecular Mechanisms in Pulmonary Hypertension and Right Ventricle Dysfunction
Pulmonary hypertension (PH) is a disorder of the pulmonary vasculature defined by increased mean pulmonary arterial pressure (mPAP) leading to right ventricle (RV) hypertrophy and dysfunction, right-sided heart failure and ultimately death. PH is a common complication of chronic lung diseases (CLD) including idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) where it is classified as Group 3 PH by the WHO. It can also be associated with cardiovascular conditions such as left-heart disease (classified as Group 2 PH) or appear on its own as pulmonary arterial hypertension (PAH) and classified as Group1 PH. In all of these cases the diagnosis of pulmonary hypertension is strongly associated with increased morbidity and mortality. The focus of this Research Topic is to enhance our understanding of the mechanisms that contribute to the pathophysiology of pulmonary hypertension and right ventricle hypertrophy.
Therapeutics in Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) continues to be a condition associated with a high morbidity and mortality despite the advances in treatment strategies over the past 25 years. Although defined by strict hemodynamic criteria, PAH is a syndrome based on diverse etiologies and pathogenesis. PAH is characterized by excessive pulmonary vascular remodeling, pulmonary arterial obstruction and elevated pulmonary vascular resistance (PVR), which result in a marked increase in right ventricle (RV) afterload. Eventually, the RV is not able to cope with the increased load and HF develops.
Pulmonary Hypertension
This book provides the framework for a singular reference in the field of pulmonary hypertension. Pulmonary vascular disease is a complex and heterogeneous condition characterized by remodeling of distal pulmonary arterioles that increases pulmonary vascular resistance to affect cardiopulmonary hemodynamic and right ventricular function adversely, resulting in a clinical syndrome of diminished exercise tolerance, shortness of breath, and heart failure-associated morbidity and mortality. Owing to the availability of novel pulmonary circulation-selective pharmacotherapies over the previous decade, the number of pulmonary hypertension patients eligible for treatment has increased substantially....
Drugs for Pregnant and Lactating Women E-Book
Logically organized and easy to use, Drugs for Pregnant and Lactating Women, 3rd Edition, is your #1 resource for details on how virtually all of today’s drugs and herbal supplements interact with pregnancy and lactation. More than just a dosing manual, this unique title by Dr. Carl P. Weiner fully explains whether each drug is FDA-approved for use by expecting or nursing mothers, is known to be safe for use, or is known to pose a danger. With up-to-date coverage of nearly 2,000 substances, it provides the thorough details you need to choose the most effective course of treatment. Uses a consistent, easy-to-follow format for each substance: generic and trade name • class • indications ...
