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

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 79; no. 4; pp. 775 - 784
• Main Authors: Butts, Brittany, Brown, Jamelle A, Denney, Jr, Thomas S, Ballinger, Scott, Lloyd, Steven G, Oparil, Suzanne, Sanders, Paul, Merriman, Tony R, Gaffo, Angelo, Singh, Jasvinder, Kelley, Eric E, Calhoun, David A, Dell'Italia, Louis J
• Format: Journal Article
• Language: English
• Published: United States 01.04.2022
• Subjects: Adult; DNA, Mitochondrial - genetics; Female; Humans; Hypertension - genetics; Male; Middle Aged; Mitochondria; Race Factors; Retrospective Studies; Xanthine Oxidase; biopsy; blood pressure; hypertension; xanthine oxidase; mitochondria
• ISSN: 0194-911X; 1524-4563; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.121.18298

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. 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. Black-resistant hypertension patients were younger (mean age 52±10 versus 59±10 years; =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 ( =0.527, =0.001) and left ventricular mass ( =0.394, =0.02) among Black but not White resistant hypertension patients. Patients with resistant hypertension had increased mtDNA DAMPs versus controls ( <0.001), with Black mtDNA DAMPS greater than Whites ( <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. 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.