HIV transgene expression impairs K+ channel function in the pulmonary vasculature

American Physiological Society 2024-02-01T08:04:52Z 2024-02-01T08:04:52Z 2018-11-01

Human immunodeficiency virus (HIV) infection is an established risk factor for pulmonary arterial hypertension (PAH); however, the pathogenesis of HIV-related PAH remains unclear. Since K+ channel dysfunction is a common marker in most forms of PAH, our aim was to analyze whether the expression of HIV proteins is associated with impairment of K+ channel function in the pulmonary vascular bed. HIV transgenic mice (Tg26) expressing seven of the nine HIV viral proteins and wild-type (WT) mice were used. Hemodynamic assessment was performed by echocardiography and catheterization. Vascular reactivity was studied in endothelium-intact pulmonary arteries. K+ currents were recorded in freshly isolated pulmonary artery smooth muscle cells (PASMC) using the patch-clamp technique. Gene expression was assessed using quantitative RT-PCR. PASMC from Tg26 mice had reduced K+ currents and were more depolarized than those from WT. Whereas voltage-gated K+ channel 1.5 (Kv1.5) currents were preserved, pH-sensitive noninactivating background currents (IKN) were nearly abolished in PASMC from Tg26 mice. Tg26 mice had reduced lung expression of Kv7.1 and Kv7.4 channels and decreased responses to the Kv7.1 channel activator L-364,373 assessed by vascular reactivity and patch-clamp experimental approaches. Although we found pulmonary vascular remodeling and endothelial dysfunction in Tg26 mice, this was not accompanied by changes in hemodynamic parameters. In conclusion, the expression of HIV proteins in vivo impairs pH-sensitive IKN and Kv7 currents. This negative impact of HIV proteins in K+ channels was not sufficient to induce PAH, at least in mice, but may play a permissive or accessory role in the pathophysiology of HIV-associated PAH.
Depto. de Farmacología y Toxicología
Fac. de Medicina
TRUE
pub

616.24; HIV; Kv7; TASK channels; Potassium channels; Pulmonary hypertension; Farmacología (Medicina); 2411.03 Fisiología Cardiovascular; journal article; VoR

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1040-0605
English

ESRCM oai:docta.ucm.es:20.500.14352/97445
Mondejar-Parreño G, Morales-Cano D, Barreira B, Callejo M, Ruiz-Cabello J, Moreno L, Esquivel-Ruiz S, Mathie A, Butrous G, Perez-Vizcaino F, Cogolludo A. HIV transgene expression impairs K+ channel function in the pulmonary vasculature. Am J Physiol Lung Cell Mol Physiol. 2018 Nov 1;315(5):L711-L723. doi: 10.1152/ajplung.00045.2018
1040-0605
1522-1504
10.1152/ajplung.00045.2018
1429626620

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