The pathophysiology of pulmonary hypertension in left heart disease

Author:

Breitling Siegfried12,Ravindran Krishnan1,Goldenberg Neil M.13,Kuebler Wolfgang M.1456

Affiliation:

1. Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada;

2. Institute for Chemistry and Biochemistry, Freie Universität Berlin, Germany;

3. Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada;

4. Institute of Physiology, Charité-Universitätsmedizin Berlin, Germany;

5. Departments of Surgery and Physiology, University of Toronto, Toronto, Ontario, Canada; and

6. German Heart Institute Berlin, Berlin, Germany

Abstract

Pulmonary hypertension (PH) is characterized by elevated pulmonary arterial pressure leading to right-sided heart failure and can arise from a wide range of etiologies. The most common cause of PH, termed Group 2 PH, is left-sided heart failure and is commonly known as pulmonary hypertension with left heart disease (PH-LHD). Importantly, while sharing many clinical features with pulmonary arterial hypertension (PAH), PH-LHD differs significantly at the cellular and physiological levels. These fundamental pathophysiological differences largely account for the poor response to PAH therapies experienced by PH-LHD patients. The relatively high prevalence of this disease, coupled with its unique features compared with PAH, signal the importance of an in-depth understanding of the mechanistic details of PH-LHD. The present review will focus on the current state of knowledge regarding the pathomechanisms of PH-LHD, highlighting work carried out both in human trials and in preclinical animal models. Adaptive processes at the alveolocapillary barrier and in the pulmonary circulation, including alterations in alveolar fluid transport, endothelial junctional integrity, and vasoactive mediator secretion will be discussed in detail, highlighting the aspects that impact the response to, and development of, novel therapeutics.

Publisher

American Physiological Society

Subject

Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology

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