Key result
Pioglitazone reduces RVSP and prevents pulmonary arterial remodeling in rats via Akt/c-Myc/TERT suppression.
Why the study?
The molecular mechanism by which PPAR-γ activation protects against TERT expression in pulmonary hypertension pathogenesis remains unknown.
Activation of PPAR-γ prevents pulmonary arterial remodeling in MCT-induced pulmonary hypertension through suppression of the Akt/c-Myc/TERT axis.
May support PPAR-γ agonism in experimental PH; leaves open translation to human disease.
Background: It has been demonstrated that elevated telomerase reverse transcriptase (TERT) expression or activity is implicated in pulmonary hypertension (PH). In addition, activation of peroxisome-proliferator-activated receptor γ (PPAR-γ) has been found to prevent PH progression. However, the molecular mechanism responsible for the protective effect of PPAR-γ activation on TERT expression in the pathogenesis of PH remains unknown. This study was performed to address these issues. Methods: Intraperitoneal injection of monocrotaline (MCT) was used to establish PH. BIBR1532 was applied to inhibit the activity of telomerase. The right ventricular systolic pressure (RVSP) and histological analysis were used to detect the development of PH. The protein levels of p-Akt, t-Akt, c-Myc and TERT were determined by western blotting. Pharmacological inhibition of TERT by BIBR1532 effectively suppressed RVSP, RVHI and the WT% in MCT-induced PH rats. Results: Pharmacological inhibition of Akt/c-Myc pathway by LY294002 diminished TERT upregulation, RVSP, RVHI and WT% in MCT-PH rats. Activation of PPAR-γ by pioglitazone inhibited p-Akt and c-Myc expressions and further downregulated TERT, thus to reduced RVSP, RVHI and WT% in MCT-treated PH rats. Conclusions: In conclusion, TERT upregulation contributes to PH development in MCT-treated rats. Activation of PPAR-γ prevents pulmonary arterial remodeling through Akt/c-Myc/TERT axis suppression.
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Hussain et al. (2023) studied Pulmonary hypertension. PPAR-γ activation (pioglitazone), BIBR1532, and LY294002 was evaluated on Right ventricular systolic pressure (RVSP), RVHI, WT%, and protein levels of p-Akt, t-Akt, c-Myc, and TERT. Activation of PPAR-γ by pioglitazone prevented pulmonary arterial remodeling and reduced right ventricular systolic pressure in MCT-treated rats through suppression of the Akt/c-Myc/TERT axis.
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