PAH is a disease caused by a constriction of the arteries in the lung, forcing the right heart ventricle to work intensely. This causes symptoms such as mitochondrial dysfunction, fatigue, angina and tachycardia, which limit a patient’s ability to perform physical exercise. As the condition progresses, even the capacity to perform everyday activities is decreased, causing a serious impact in patients’ quality of life. Eventually, the heart can no longer function and the individual dies.
The narrowing of the blood arteries seen in PAH is caused by an uncontrollable growth of cells in the arteries’ walls, resembling the growth of cancer cells. Furthermore, these cells are insulin resistant, as seen in diabetes. Previous research conducted by Evangelos Mickelakis’ team had suggested that mitochondria are involved in the development of PAH, diabetes, and cancer.
Researcher Roxane Paulin stated that the results from their unbiased cohort study in 162 PAH patients and controls, published in journal Cell Metabolism, entitled, “Sirtuin 3 Deficiency Is Associated with Inhibited Mitochondrial Function and Pulmonary Arterial Hypertension in Rodents and Humans,” shows that mice lacking sirtuin 3 (SIRT3), a mitochondrial deacetylase, is a critical regulator of metabolic homeostasis in pulmonary artery smooth muscle cells (PASMC).
Findings indicate that loss of function of SIRT3 polymorphism, linked to metabolic syndrome, promotes the development of PAH. Furthermore, the researchers found indirect indices of insulin resistance in Sirt3KO skeletal muscle, which are similar to the metabolic features seen in PAH patients.
To enhance the potential therapeutic implications in humans of these findings, this study showed that SIRT3 restoration in a rat PAH model decreases the phenotype expression of PAH. Thus, adenoviral mediated correction of SIRT3 deficiency can be further explored as a treatment option.
By prospectively unraveling a metabolic basis implied in the development of PAH, there is the potential to unlock better diagnosis and treatment for this medical condition.
These new findings offer encouraging research news for the PH community this November, which marks the Pulmonary Hypertension awareness month.
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