The lungs are the primary organs affected in LHD (left heart disease). Increased left atrial pressure leads to pulmonary alveolar–capillary stress failure, resulting in cycles of alveolar wall injury and repair. The reparative process causes the proliferation of MYFs (myofibroblasts) with fibrosis and extracellular matrix deposition, resulting in thickening of the alveolar wall. Although the resultant reduction in vascular permeability is initially protective against pulmonary oedema, the process becomes maladaptive causing a restrictive lung syndrome with impaired gas exchange. This pathological process may also contribute to PH (pulmonary hypertension) due to LHD. Few clinical trials have specifically evaluated lung structural remodelling and the effect of related therapies in LHD. Currently approved treatment for chronic HF (heart failure) may have direct beneficial effects on lung structural remodelling. In the future, novel therapies specifically targeting the remodelling processes may potentially be utilized. In the present review, we summarize data supporting the clinical importance and pathophysiological mechanisms of lung structural remodelling in LHD and propose that this pathophysiological process should be explored further in pre-clinical studies and future therapeutic trials.
- heart failure
- left heart disease
- pulmonary heart disease
- pulmonary hypertension
Abbreviations: ACE, angiotensin-converting enzyme; ACEI, ACE inhibitor; ARB, angiotensin receptor blocker; DLCO, lung carbon monoxide diffusion; DM, membrane gas conductance; ECM, extracellular matrix; ENaC, epithelium Na+ channel; ERA, endothelin receptor antagonist; HF, heart failure; LHD, left heart disease; LV, left ventricular; MYF, myofibroblast; PAH, pulmonary arterial hypertension; PAP, pulmonary artery pressure; PASP, pulmonary artery systolic pressure; PCWP, pulmonary capillary wedge pressure; PDE5, phosphodiesterase 5; PH, pulmonary hypertension; PVR, pulmonary vascular resistance; RAS, renin–angiotensin system; RV, right ventricular; SMA, smooth muscle actin; SPB, surfactant protein type B; TGF, transforming growth factor; TPG, transpulmonary pressure gradient; VA, alveolar volume; VC, capillary volume; WHO, World Health Organization; V̇CO2, carbon dioxide production; V̇E, expired minute ventilation; V̇O2, oxygen consumption
- © The Authors Journal compilation © 2014 Biochemical Society