The pathobiology of pulmonary hypertension: Smooth muscle cells and ion channels

Evangelos D. Michelakis, Edward K Weir

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Chronic hypoxic pulmonary arterial hypertension, APAH, and PPAH are characterized by vasoconstriction and vascular remodeling and are associated with decreased Kv currents in PA smooth muscle cells. Although Kv2.1 is less well studied, it seems that Kv1.5 is particularly important in the pulmonary circulation in animals and humans because it has been implicated in physiologic phenomena (HPV) and all of the aforementioned pulmonary hypertensive disorders. This occurrence is perhaps because of the fact that it controls Em in the PA smooth muscle cells and it has a short turnover half time. It is also certain that the pathogenesis of PPAH is multifactorial and not a result of a single abnormality. The recently discovered "PPAH gene" in chromosome 2q in patients with familial PPAH (6%-12% of patients) does not seem to encode for any Kv channels. Kv1.5 abnormalities, however, are likely to be a strong predisposing factor that, in association with others such as endothelial dysfunction, anorexigen use, or viral infections, will initiate a process that eventually leads to PPAH. The selective Kv1.5 down-regulation leaves wide open the door to replacement gene therapy in pulmonary hypertension research.

Original languageEnglish (US)
Pages (from-to)419-432
Number of pages14
JournalClinics in Chest Medicine
Issue number3
StatePublished - Jan 1 2001
Externally publishedYes

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