Biomolecules
α-Lipoic Acid, with or Without Ambrisentan, Attenuates Experimental Pulmonary Arterial Hypertension: Associations with AMPK/mTOR/NF-κB Signaling and Kallistatin
By Seyhan Ayik, Mustafa Hüz, Zeynep Ulutaş and 8 others.
Abstract
Background
Pulmonary arterial hypertension (PAH) is characterized by progressive pulmonary vascular remodeling driven by excessive cellular proliferation and inflammation. Targeting both vasoconstriction and vascular remodeling represents a key therapeutic strategy. Alpha-lipoic acid (α-LA), a metabolic and anti-inflammatory modulator, is associated with modulation of AMPK/mTOR/NF-κB signaling, whereas ambrisentan (AMB) is an endothelin receptor antagonist with established vasodilatory effects. We investigated the beneficial effects of α-LA and AMB, administered alone or in combination, in a monocrotaline (MCT)-induced PAH rat model.
Methods
Male rats were randomly assigned to control, MCT, α-LA, AMB, and α-LA + AMB groups. PAH was induced by a single subcutaneous injection of monocrotaline (60 mg/kg). Treatments were administered between days 22 and 35. Echocardiographic measurements were obtained, and histopathological, immunohistochemical, and biochemical analyses were performed in lung and cardiac tissues and in serum. Sample sizes analyzed per outcome were: echocardiography (Control: n = 10, MCT: n = 10, α-LA: n = 8, AMB: n = 9, α-LA + AMB: n = 10), histology (n = 10/group), RVSP (Control: n = 7, MCT: n = 8, α-LA: n = 8, AMB: n = 7, α-LA + AMB: n = 9), Fulton index (Control: n = 10, MCT: n = 10, α-LA: n = 12, AMB: n = 9, α-LA + AMB: n = 10), and ELISA (n = 8/group). Statistical analyses were performed using a web-based statistical software, applying one-way ANOVA or the Kruskal–Wallis test according to data distribution. Results were considered statistically significant at p < 0.05.