Transmission electron microscopic analysis of mitochondria changes in pulmonary arterial hypertension

Abstract

Mitochondria are dynamic organelles, which play crucial roles in many cellular processes. Their severe damage results in alterations of other ultrastructural components and leads to loss of cellular function. In pulmonary hypertension (PH), increasing of the pulmonary vascular resistance puts the strain on the right ventricle, leading to the demand for ATP production by mitochondria to ensure cardiomyocyte function. The failure of cardiac pump increases the peripheral resistance by inducing the neurohormonal activation and influences the skeletal muscle structure and function, leading to the muscle weakness. In a rat PH model, our previous morphometric study reported changes in the mitochondrial types. Type I–II mitochondria are defined as mitochondria with the preserved ultrastructure and Type III–IV mitochondria are defined as mitochondria with the severe cristae damage that are not able to produce the required amount of ATP for energy‐depended processes in cardiomyocytes. Fischer rats had 100% mortality because of right heart failure in PH. In their RV cardiomyocytes, the types III–IV of mitochondria were predominant, along with a drastic decrease in coefficient of energy efficiency of mitochondria (CEEM), while in LV types II–III of mitochondria were present. Whereas the SD rats that do not die of PH, mostly had mitochondria Type I–II in RV and LV, along with slight decrease in CEEM in RV. In both strains of rats with PH, the treatment with a Bcl‐2 inhibitor, Navitoclax (ABT‐263), lead to severe damage of the mitochondria structure, causing rats to die because of hearth failure. The transmission electron microscopy (TEM) analysis of mitochondria in skeletal muscle cells in PH revealed the decrease in mitochondria volume and the damage to the mitochondria structure. In skeletal muscle cells, Type III mitochondria were present in rats, which correlates with the reduction in aerobic capacities. These results suggest that the ultrastructural defects in mitochondria in both cardiac and skeletal muscle in PH impact the development of the hearth failure and death, thus PH can be described as a systemic disease.Support or Funding InformationNIHThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.