Cholesterol Regulation of Pulmonary Endothelial Calcium Homeostasis

Abstract

Cholesterol is a key structural component and regulator of lipid raft signaling platforms critical for cell function. Such regulation may involve changes in the biophysical properties of lipid microdomains or direct protein-sterol interactions that alter the function of ion channels, receptors, enzymes, and membrane structural proteins. Recent studies have implicated abnormal membrane cholesterol levels in mediating endothelial dysfunction that is characteristic of pulmonary hypertensive disorders, including that resulting from long-term exposure to hypoxia. Endothelial dysfunction in this setting is characterized by impaired pulmonary endothelial calcium entry and an associated imbalance that favors production vasoconstrictor and mitogenic factors that contribute to pulmonary hypertension. Here we review current knowledge of cholesterol regulation of pulmonary endothelial Ca²⁺ homeostasis, focusing on the role of membrane cholesterol in mediating agonist-induced Ca²⁺ entry and its components in the normal and hypertensive pulmonary circulation.

Keywords: Caveolin-1; Chronic hypoxia; Epicholesterol; Orai1; Store-operated Ca(2+) entry; T-type voltage-gated Ca(2+) channel.