Mitochondria DNA mutations cause sex-dependent development of XXXX and alterations in cardiovascular function.

@entity46372 @entity101 @entity19 @entity1184 @entity54030 @entity1240 @entity123 @entity67 @entity65
UNASSIGNED: Aging is associated with conduit artery stiffening that is a risk factor for and can precede @entity101 and @entity67 . Increases in mitochondria DNA (mtDNA) frequency have been correlated with aging. @entity19 with a mutation in the encoding domain ( @entity46372 ) of a proof-reading deficient version of mtDNA polymerase-y ( @entity54030 ) have musculoskeletal features of @entity1240 and a shortened lifespan. However, few studies using these @entity19 have investigated the effects of mtDNA mutations on cardiovascular function. We hypothesized that the proof-reading deficient mtDNA @entity54030 leads to arterial stiffening, @entity101 , and @entity123 . Ten to twelve month-old @entity46372 @entity19 (n=13) and age- and sex-matched wild-type controls (n=13) were catheterized for hemodynamic and ventricular function measurements. Left common carotid arteries (LCCA) were harvested for mechanical tests followed by histology. Male @entity46372 @entity19 had pulmonary and systemic @entity101 , arterial stiffening, larger LCCA diameter (701  45 vs. 597  60 m), shorter LCCA axial length (8.96  0.56 vs. 10.10  0.80mm), and reduced hematocrit (29.1  6.1 vs. 41.3  8.1; all p<0.05). Male and female @entity46372 @entity19 had @entity1184 (p<0.05). Female @entity46372 @entity19 did not have significant increases in pressure or arterial stiffening, suggesting that the mechanisms of @entity101 or arterial stiffening from mtDNA mutations differ based on sex. Our results lend insight into the mechanisms of age-related @entity65 and may point to novel treatment strategies to address cardiovascular mortality in the elderly.
