Endothelial Dysfunction in Pulmonary Hypertension

Fonseca, Johnson Campideli; Balzano, C.D. Martínez; León, Roberto Sánchez de

doi:10.1016/s1579-2129(06)60247-4

Cited by 1 publication

(1 citation statement)

References 27 publications

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“…This finding coincides with our experimental results. Endothelial dysfunction occurs in the early stages of PH and is reflected by reduction in the secretion of vasodilators, such as NO and prostacyclin, and overproduction of vasoconstrictive factors, such as ET-1 and thromboxane [ 33 ]. Reduced generation of NO, due to reduced synthesis of eNOS in ECs, attenuates its protective effect against PH, including vasodilation and inhibition of proliferation of pulmonary SMCs [ 9 , 10 ].…”

Section: Discussionmentioning

confidence: 99%

miR-21-Mediated Endothelial Senescence and Dysfunction Are Involved in Cigarette Smoke-Induced Pulmonary Hypertension through Activation of PI3K/AKT/mTOR Signaling

He,

Shao,

Cheng

et al. 2024

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Smoking is a pathogenic factor for pulmonary hypertension (PH). Our previous study showed that serum miR-21 levels are elevated in smokers. miR-21 is considered as engaged in the PH process; however, its mechanisms remain unclear. In this investigation, we found that in the lung tissue of smoking-induced PH patients, the levels of miR-21 and aging markers (p21 and p16) were upregulated, and the function of pulmonary vascular endothelial cells was also impaired. Exposure of mice to cigarette smoke (CS) for four months caused similar changes in lung tissues and increased pulmonary arterial pressure, which were attenuated by knockout of miR-21. Further, human umbilical vein endothelial cells (HUVECs) exposed to cigarette smoke extract (CSE) revealed upregulation of miR-21 levels, depression of PTEN, activation of PI3K/AKT/mTOR signaling, an increase in senescence indexes, and enhanced dysfunction. Inhibiting miR-21 overexpression reversed the PTEN-mTOR signaling pathway and prevented senescence and dysfunction of HUVECs. In sum, our data indicate that miR-21-mediated endothelial senescence and dysfunction are involved in CS-induced PH through the activation of PI3K/AKT/mTOR signaling, which suggests that selective miR-21 inhibition offers the potential to attenuate PH.

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Section: Discussionmentioning

confidence: 99%