Mitochondrial Damage May Explain the Increased Incidence of Hypertension in Black Adults

Increased plasma concentration of the enzyme xanthine oxidase (XO) and the resulting mitochondrial DNA damage that it can cause may explain why Blacks have a significantly higher incidence of hypertension than their White counterparts.

Investigators at the University of Alabama (Birmingham, USA) had previously reported that increased plasma XO activity in patients with resistant hypertension could cause mitochondrial DNA damage and promote release of fragments called mitochondrial DNA damage-associated molecular patterns (mtDNA DAMPs). Xanthine oxidase is widely distributed in the heart, liver, gut, lung, kidney and brain, as well as in blood plasma. In its normal metabolic function, it generates oxygen radicals as a byproduct, including hydrogen peroxide and superoxide, which are reactive oxygen species that can damage DNA.

Considering that Black adults in the United States have one of the highest rates of hypertension in the world and have a 50% increased incidence of heart failure as compared to Whites, the investigators examined the importance of racial differences in XO activity and mtDNA DAMPs in adults with resistant hypertension.

The experimental cohort for this study included 91 resistant hypertension patients, 44% of whom were Black, and 37 controls with normal blood pressures. The resistant hypertension group all had blood pressures above 140/90 millimeters of mercury (mmHg), and all were on four or more medications for treatment of their high blood pressure.

Results revealed that Black resistant hypertension patients were younger (mean age 52±10 versus 59±10 years), with higher XO activity and left ventricular wall thickness, and worse diastolic dysfunction than White resistant hypertension patients. Urinary sodium excretion was positively related to left ventricular end-diastolic volume and left ventricular mass among Black but not White resistant hypertension patients. Patients with resistant hypertension had increased mtDNA DAMPs versus controls, with Black mtDNA DAMPS greater than Whites.

Transmission electron microscopy of skeletal muscle biopsies in resistant hypertension patients demonstrated mitochondrial damage such as cristae lysis, myofibrillar loss, large lipid droplets, and glycogen accumulation.

"Xanthine oxidase activation may set up a feed-forward cycle of mitochondrial damage, mitochondrial reactive oxygen species production, mtDNA DAMP release, and inflammation in the pathogenesis of hypertension end-organ injury," said senior author Dr. Louis J. Dell'Italia, professor emeritus of cardiovascular disease at the University of Alabama. "These results warrant a larger study that includes metabolic syndrome and xanthine oxidase as a potential therapeutic target to reduce mitochondrial damage and attenuate left ventricular diastolic dysfunction in Black adults with resistant hypertension. Although Black adults have the highest death rate for heart failure, they are consistently underrepresented in clinical trials. The greater heart failure burden among Black adults calls for further work to discover effective preventive and therapeutic strategies for this higher-risk population."

The study was published in the February 15, 2022, online edition of the journal Hypertension.

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