Figure 6.

Effects of resveratrol in the PAH phenotype. Monocrotaline-induced PAH is a disease characterized by a progressive remodeling of the pulmonary vasculature, as a consequence of excessive proliferation and migration of pulmonary artery endothelial and smooth muscle cells. With the progression of the disease, the increase of the mean pulmonary artery pressure leads to a chamber pressure overload in the right ventricle (RV). When the optimal RV-arterial coupling is lost, the RV systolic function cannot remain matched to the afterload, and subsequently, dilation of the RV occurs, as well as diastolic dysfunction, secondary to myocardial fibrosis and sarcomeric stiffening. These changes ultimately lead to right heart failure and death. Even though the administration of resveratrol decreased the pathological remodeling of the pulmonary vasculature, it did not change the afterload for the RV (represented in the figure as a change in arrows' thickness). Nevertheless, resveratrol was able to protect directly the RV, improving its function, evidentiated with microscopic changes: less fibrosis, decreased cardiomyocyte area and volume and better cell function, with increased cell shortening, increasing SIRT1-mediated deacetylation, and decreasing inflammatory and remodeling markers. The arrows in the PAH model indicate the changes compared to the CTRL group; the arrows in the PAH+RES model indicate the changes compared to the PAH group.