Bernal-Ramirez 2021 Oxid Med Cell Longev
| Bernal-Ramirez J, Silva-Platas C, Jerjes-Sanchez C, Ramos-Gonzalez MR, Vazquez-Garza E, Chapoy-Villanueva H, Ramirez-Rivera A, Zarain-Herzberg A, Garcia N, Garcia-Rivas G (2021) Resveratrol prevents right ventricle dysfunction, calcium mishandling, and energetic failure via SIRT3 stimulation in pulmonary arterial hypertension. Oxid Med Cell Longev 2021:9912434. |
Bernal-Ramirez Judith, Silva-Platas Christian, Jerjes-Sanchez Carlos, Ramos-Gonzalez Martin R., Vazquez-Garza Eduardo, Chapoy-Villanueva Hector, Ramirez-Rivera Alicia, Zarain-Herzberg Angel, Garcia Noemi, Garcia-Rivas Gerardo (2021) Oxid Med Cell Longev
Abstract: Pulmonary arterial hypertension (PAH) is characterized by pulmonary vessel remodeling; however, its severity and impact on survival depend on right ventricular (RV) failure. Resveratrol (RES), a polyphenol found in red wine, exhibits cardioprotective effects on RV dysfunction in PAH. However, most literature has focused on RES protective effect on lung vasculature; recent finding indicates that RES has a cardioprotective effect independent of pulmonary arterial pressure on RV dysfunction, although the underlying mechanism in RV has not been determined. Therefore, this study is aimed at evaluating sirtuin-3 (SIRT3) modulation by RES in RV using a monocrotaline- (MC-) induced PAH rat model. Myocyte function was evaluated by confocal microscopy as cell contractility, calcium signaling, and mitochondrial membrane potential (ΞΞ¨m); cell energetics was assessed by high-resolution respirometry, and western blot and immunoprecipitation evaluated posttranslational modifications. PAH significantly affects mitochondrial function in RV; PAH is prone to mitochondrial permeability transition pore (mPTP) opening, thus decreasing the mitochondrial membrane potential. The compromised cellular energetics affects cardiomyocyte function by decreasing sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) activity and delaying myofilament unbinding, disrupting cell relaxation. RES partially protects mitochondrial integrity by deacetylating cyclophilin-D, a critical component of the mPTP, increasing SIRT3 expression and activity and preventing mPTP opening. The preserved energetic capability rescues cell relaxation by maintaining SERCA activity. Avoiding Ca2+ transient and cell contractility mismatch by preserving mitochondrial function describes, for the first time, impairment in excitation-contraction-energetics coupling in RV failure. These results highlight the importance of mitochondrial energetics and mPTP in PAH.
β’ Bioblast editor: Reiswig R β’ O2k-Network Lab: MX San Pedro Garcia-Rivas G
Labels: MiParea: Respiration, Pharmacology;toxicology
Organism: Rat
Tissue;cell: Heart
Preparation: Isolated mitochondria
Coupling state: OXPHOS, ET
Pathway: S
HRR: Oxygraph-2k
2021-07
