Association of Phagocytic NADPH Oxidase Activity With Hypertensive Heart Disease: A Role for Cardiotrophin-1?

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 63; no. 3; pp. 468 - 474
• Main Authors: Moreno, María U., San José, Gorka, Pejenaute, Álvaro, Landecho, Manuel F., Díez, Javier, Beloqui, Óscar, Fortuño, Ana, Zalba, Guillermo
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 01.03.2014; Lippincott Williams & Wilkins
• Subjects: Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cytokines - blood; Cytokines - physiology; Disease Progression; Echocardiography; Female; Follow-Up Studies; Heart Ventricles - diagnostic imaging; Heart Ventricles - physiopathology; Humans; Hypertension - complications; Hypertension - metabolism; Hypertension - physiopathology; Hypertrophy, Left Ventricular - etiology; Hypertrophy, Left Ventricular - metabolism; Hypertrophy, Left Ventricular - physiopathology; Male; Medical sciences; Middle Aged; Multienzyme Complexes - biosynthesis; NADH, NADPH Oxidoreductases - biosynthesis; Hypertension; NADPH; cardiotrophin 1; Enzyme; Oxidase; hypertrophy, left ventricular; Cardiovascular disease; Left ventricle; Hyperoxides; Association; Heart disease; NADPH oxidase; Oxidoreductases; Circulatory system; Cardiology; superoxides; Phagocytosis; Hypertrophy; hypertension
• ISSN: 0194-911X; 1524-4563; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.113.01470

Left ventricular hypertrophy (LVH) is an independent marker of mortality in hypertension. Although the mechanisms contributing to LVH are complex, inflammation and oxidative stress may favor its development. We analyzed the association of the phagocytic NADPH oxidase–mediated superoxide anion release and LVH in patients with essential hypertension and the role of cardiotrophin-1 (CT-1) and interleukin-6 (IL-6), cytokines implicated in cardiac growth. Blood pressure, echocardiography data, and serum CT-1 and IL-6 levels were obtained in 140 subjects18 normotensives without LVH, 42 hypertensives without LVH, and 80 hypertensives with LVH. The NADPH oxidase–dependent superoxide production was assessed by chemiluminescence in peripheral blood mononuclear cells. Peripheral blood mononuclear cells were stimulated with CT-1 in vitro. Superoxide anion production by peripheral blood mononuclear cells associated with LVH and correlated with the left ventricular mass index. Serum CT-1 and IL-6 levels, which associated with the left ventricular mass index, correlated with superoxide production. Serum CT-1 and IL-6 levels were correlated. CT-1 stimulated NADPH oxidase superoxide production in peripheral blood mononuclear cells, which resulted in an increased release of IL-6. Our results show that superoxide anion production by the phagocytic NADPH oxidase associates with hypertensive heart disease, being significantly enhanced in hypertensive patients with LVH. This may be attributable to the activation of the NADPH oxidase by CT-1 and the subsequent release of IL-6. The phagocytic NADPH oxidase may be a therapeutic target in hypertensive heart disease.