Racial Differences in XO (Xanthine Oxidase) and Mitochondrial DNA Damage-Associated Molecular Patterns in Resistant Hypertension

Abstract

Background: We previously reported increased plasma XO (xanthine oxidase) activity in patients with resistant hypertension. Increased XO can cause mitochondrial DNA damage and promote release of fragments called mitochondrial DNA damage-associated molecular patterns (mtDNA DAMPs). Here, we report racial differences in XO activity and mtDNA DAMPs in Black and White adults with resistant hypertension. Methods: This retrospective study includes 91 resistant hypertension patients (44% Black, 47% female) with blood pressure >140/90 mm Hg on ≥4 medications and 37 normotensive controls (30% Black, 54% female) with plasma XO activity, mtDNA DAMPs, and magnetic resonance imaging of left ventricular morphology and function. Results: Black-resistant hypertension patients were younger (mean age 52±10 versus 59±10 years; P =0.001), with higher XO activity and left ventricular wall thickness, and worse diastolic dysfunction than White resistant hypertension patients. Urinary sodium excretion (mg/24 hour per kg) was positively related to left ventricular end-diastolic volume ( r =0.527, P =0.001) and left ventricular mass ( r =0.394, P =0.02) among Black but not White resistant hypertension patients. Patients with resistant hypertension had increased mtDNA DAMPs versus controls ( P <0.001), with Black mtDNA DAMPS greater than Whites ( P <0.001). Transmission electron microscopy of skeletal muscle biopsies in resistant hypertension patients demonstrates mitochondria cristae lysis, myofibrillar loss, large lipid droplets, and glycogen accumulation. Conclusions: These data warrant a large study to examine the role of XO and mitochondrial mtDNA DAMPs in cardiac remodeling and heart failure in Black adults with resistant hypertension.

Extracellular vesicle mitochondrial DNA levels are associated with race and mitochondrial DNA haplogroup

“…Previous studies have suggested that ccf-mtDNA may be associated with spontaneous hypertension in rats 14 , in resistant hypertension in African American men and women 13 as well as in the hypertension-related condition, pre-eclampsia. 55 There is also some evidence that ccf-mtDNA is present in the urine hypertensive African American patients.…”

“… 11 Few studies have explored the role of ccf-mtDNA in the context of hypertension. 7 , 12 , 13 , 14 mtDNA levels of the mitochondrially encoded NADH dehydrogenase 1 and 6 ( MT-ND1 , MT-ND6 ) are significantly higher in the plasma of patients with resistant hypertension (n = 91) compared with controls (n = 37), with mtDNA levels significantly higher in Black patients (n = 40) compared with White patients (n = 51) with resistant hypertension. 13 McCarthy et al.…”

“… 7 , 12 , 13 , 14 mtDNA levels of the mitochondrially encoded NADH dehydrogenase 1 and 6 ( MT-ND1 , MT-ND6 ) are significantly higher in the plasma of patients with resistant hypertension (n = 91) compared with controls (n = 37), with mtDNA levels significantly higher in Black patients (n = 40) compared with White patients (n = 51) with resistant hypertension. 13 McCarthy et al. have shown that levels of ccf-mtDNA in rats, specifically the cytochrome b , mitochondrial ( mt-Cytb ), and mt-Nd6 gene regions, are elevated in male rats with spontaneous hypertension (n = 3–8).…”

The Effects of Exercise on Telomere Length in Persons With Heart Failure

“…Considering the known role of inflammation and oxidative stress in persons with HF, 5,42 more work is needed to better understand the role of cellular aging in the context of the HF inflammatory milieu. Telomerase dysfunction and shorter leukocyte telomere length are associated with increased cardiovascular risk and mortality 43 and should be considered as part of the pathophysiological changes that lead to cardiovascular disease risk and development.…”

Maternal nano-titanium dioxide inhalation exposure alters placental cyclooxygenase and oxidant balance in a sexually dimorphic manner

“…One unit of activity (U) was defined as 1 μmole/min urate formed at 37 °C and pH 7.4. Results were expressed as a concentration relative to total sample protein content [ 35 ]. Inter- and intra-assay variability were less than 10 %.…”