Open AccessAssociated Inflammation or Increased Flow‐Mediated Shear Stress, but not Pressure Alone, Disrupts Endothelial Caveolin‐1 in Infants with Pulmonary Hypertension
Author(s) -
Dereddy Narendra,
Huang Jing,
Erb Markus,
Guzel Sibel,
Wolk John H,
Sett Suvro S,
Gewitz Michael H,
Mathew Rajamma
Publication year - 2012
Publication title -
pulmonary circulation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.791
H-Index - 40
ISSN - 2045-8940
DOI - 10.4103/2045-8932.105038
Subject(s) - medicine , caveolin 1 , pulmonary hypertension , endothelial activation , inflammation , endothelium , lung , pathology , endothelial dysfunction , caveolin , endothelial stem cell , pulmonary artery , immunology , endocrinology , caveolae , microbiology and biotechnology , biology , signal transduction , biochemistry , in vitro
Endothelial caveolin‐1 loss is an important feature of pulmonary hypertension (PH); the rescue of caveolin‐1 abrogates experimental PH. Recent studies in human PH suggest that the endothelial caveolin‐1 loss is followed by an enhanced expression of caveolin‐1 in smooth muscle cells (SMC) with subsequent neointima formation. In order to evaluate caveolin‐1 expression in infants with PH, we examined the available clinical histories, hemodynamic data, and the expression of caveolin‐1, PECAM‐1, vWF, and smooth muscle α‐actin in the lung biopsy/autopsy specimens obtained from infants with congenital heart disease (CHD, n = 8) and lung disease (n = 9). In CHD group, PH associated with increased pulmonary blood flow exhibited loss of endothelial caveolin‐1 and PECAM‐1 in pulmonary arteries; additional vWF loss was associated with enhanced expression of caveolin‐1 in SMC. In the absence of PH, increased or decreased pulmonary blood flow did not disrupt endothelial caveolin‐1, PECAM‐1, or vWF; nor was there any enhanced expression of caveolin‐1 in SMC. In Lung Disease + PH group, caveolin‐1, PECAM‐1, and vWF were well preserved in seven infants, and importantly, SMC in these arteries did not exhibit enhanced caveolin‐1 expression. Two infants with associated inflammatory disease exhibited loss of endothelial caveolin‐1 and PECAM‐1; additional loss of vWF was accompanied by enhanced expression of caveolin‐1 in SMC. Thus, associated flow‐induced shear stress or inflammation, but not elevated pulmonary artery pressure alone, disrupts endothelial caveolin‐1. Subsequent vWF loss, indicative of extensive endothelial damage is associated with enhanced expression of caveolin‐1 in SMC, which may worsen the disease.