Endothelial dysfunction and lung capillary injury in cardiovascular diseases

Prog Cardiovasc Dis. 2015 Mar-Apr;57(5):454-62. doi: 10.1016/j.pcad.2014.11.003. Epub 2014 Nov 12.


Cardiac dysfunction of both systolic and diastolic origins 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 alveolar-capillary 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 limitation 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.

Keywords: Alveolar-capillary unit; Endothelial dysfunction; Lung capillaries.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood-Air Barrier / pathology
  • Blood-Air Barrier / physiopathology*
  • Capillaries / pathology
  • Capillaries / physiopathology*
  • Capillary Permeability
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiopathology*
  • Heart Failure / complications*
  • Heart Failure / diagnosis
  • Heart Failure / physiopathology
  • Heart Failure / therapy
  • Humans
  • Hypertension, Pulmonary / etiology
  • Hypertension, Pulmonary / physiopathology
  • Lung / blood supply*
  • Lung Diseases / diagnosis
  • Lung Diseases / etiology*
  • Lung Diseases / physiopathology
  • Lung Diseases / therapy
  • Prognosis
  • Pulmonary Gas Exchange
  • Risk Factors
  • Vascular Remodeling*