Endothelial Dysfunction and Lung Capillary Injury in Cardiovascular Diseases

Abstract

Cardiac dysfunction of both systolic and diastolic origin leads to increased left atrial pressure, lung capillary injury and increased resistance to gas transfer. Acutely, pressure-induced trauma disrupts the endothelial and alveolar anatomical configuration and definitively causes an impairment of cellular pathways involved in fluid-flux regulation and gas exchange efficiency, a process well identified as stress failure of the alveolarcapillary membrane. In chronic heart failure (HF), additional stimuli other than pressure may trigger the true remodeling process of capillaries and small arteries characterized by endothelial dysfunction, proliferation of myofibroblasts, fibrosis and extracellular matrix deposition. In parallel there is a loss of alveolar gas diffusion properties due to the increased path from air to blood (thickening of extracellular matrix) and loss of fine molecular mechanism involved in fluid reabsorption and clearance. Deleterious changes in gas transfer not only reflect the underlying lung tissue damage but also portend independent prognostic information and may play a role in the pathogenesis of exercise limitations and ventilatory abnormalities observed in these patients. Few currently approved treatments for chronic HF have the potential to positively affect structural remodeling of the lung capillary network; angiotensin-converting enzyme inhibitors are one of the few currently established options. Recently, more attention has been paid to novel therapies specifically targeting the nitric oxide pathway as a suitable target to improve endothelial function and permeability as well as alveolar gas exchange properties.

Exhaled Acetone Concentration Is Related to Hemodynamic Severity in Patients With Non-Ischemic Chronic Heart Failure

“…25 In this study population, although EAC showed a positive relationship with blood TKB level and PCWP, the blood TKB level did not show a significant direct relationship with PCWP. PCWP, an indicator of pulmonary congestion, might be associated with EAC through the blood-gas barrier, in addition to the increased blood ketone body level in HF.…”

Maresin1 stimulates alveolar fluid clearance through the alveolar epithelial sodium channel Na,K-ATPase via the ALX/PI3K/Nedd4-2 pathway

“…30,37 Impairment of Na,K-ATPase function appears to be a hallmark during lung injury even in a preclinical stage. 30,35,38 In our study, we demonstrated that MaR1 not only increased Na,K-ATPase expression in rat lung tissues and primary ATII cells after LPS challenge by western blotting, immunohistochemistry, and confocal laser-scanning microscopy measurement, but also upregulation of Na,K-ATPase activity in vivo. Altogether, our data from the lung tissues and cell culture indicate that MaR1 promotes AFC through both of the essential mechanisms of ENaC and Na,K-ATPase.…”

Organ dysfunction, injury and failure in acute heart failure: from pathophysiology to diagnosis and management. A review on behalf of the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

“…Repetitive or severe decompensations may result in cardiopulmonary remodelling (i.e. endothelial dysfunction, proliferation of myofibroblasts, fibrosis and thickening of the extracellular matrix) with an impairment in alveolar gas diffusion properties, pulmonary vasoconstriction and, finally, pulmonary hypertension . This process also leads to the restrictive ventilation pattern observed in CHF .…”