Dan Wang1, Joseph K Melancon2, Jennifer Verbesey2, Haihong Hu3, Chenglong Liu3, Shakil Aslam1, Mary Young3, Christopher S Wilcox1. 1. Hypertension, Kidney and Vascular Research Center and the Division of Nephrology and Hypertension, Georgetown University, USA. 2. Transplant Institute, Georgetown University, USA. 3. Division of Infectious Disease and the Metropolitan Washington Women's HIV Study group, Georgetown University, Washington, USA.
Abstract
11 BACKGROUND: The prevalence of cardiovascular disease is increased with human immunodeficiency virus (HIV) infection, but the mechanism is unclear. We hypothesized that HIV increases microvascular reactive oxygen species, thereby impairing endothelial function and enhancing contractility. 12 METHOD: Subcutaneous microarterioles were isolated from gluteal skin biopsies in premenopausal, African American, HIV positive women receiving effective anti-retroviral therapy, but without cardiovascular risk factors except for increased body mass index (n=10) and healthy matched controls (n=10). The arterioles were mounted on myographs, preconstricted and relaxed with acetylcholine for: endothelium-dependent relaxation, endothelium-dependent relaxation factor (nitric oxide synthase-dependent relaxation), endothelium-dependent hyperpolarizing factor (potassium-channel dependent relaxation) and endothelium-independent relaxation (nitroprusside). Contractions were tested to endothelium-dependent contracting factor (acetylcholine contraction with blocked relaxation); phenylephrine, U-46,619 and endothelin-1. Plasma L-arginine and asymmetric dimethylarginine were measured by high performance capillary electrophoresis. 13 RESULTS: The micro-arterioles from HIV positive women had significantly (% change in tension; P<0.05) reduced acetylcholine relaxation (-51 ± 6 vs. -78 ± 3%), endothelium-dependent relaxation factor (-28 ± 4 vs. -39 ± 3%), endothelium-dependent hyperpolarizing factor (-17 ± 4 vs. -37 ± 4%) and decreased nitric oxide activity (0.16 ± 0.03 vs. 0.70 ± 0.16 Δ unit) but unchanged nitroprusside relaxation. They had significantly enhanced endothelium-dependent contracting factor (+21 ± 6 vs. +7 ± 2%) and contractions to U-46,619 (+164 ± 10 vs. +117 ± 11%) and endothelin-1(+151 ± 12 vs. +97 ± 9%), but not to phenylephrine. There was enhanced reactive oxygen species with acetylcholine (0.11 ± 0.02 vs. 0.05 ± 0.01 Δ unit; P<0.05) and endothelin-1 (0.31 ± 0.06 vs. 0.10 ± 0.02 Δ unit; P<0.05). Plasma L-arginine: assymetric dimethyl arginine rates was reduced (173 ± 12 vs. 231 ± 6 μmol·μmol-1, P<0.05). 14 CONCLUSION: Premenopausal HIV positive womenhad microvascular oxidative stress with severe endothelial dysfunction and reduced nitric oxide and arginine: assymetric dimethylarginine ratio but enhanced endothelial, thromboxane and endothelin contractions. These microvascular changes may herald later cardiovascular disease.
11 BACKGROUND: The prevalence of cardiovascular disease is increased with human immunodeficiency virus (HIV) infection, but the mechanism is unclear. We hypothesized that HIV increases microvascular reactive oxygen species, thereby impairing endothelial function and enhancing contractility. 12 METHOD: Subcutaneous microarterioles were isolated from gluteal skin biopsies in premenopausal, African American, HIV positive women receiving effective anti-retroviral therapy, but without cardiovascular risk factors except for increased body mass index (n=10) and healthy matched controls (n=10). The arterioles were mounted on myographs, preconstricted and relaxed with acetylcholine for: endothelium-dependent relaxation, endothelium-dependent relaxation factor (nitric oxide synthase-dependent relaxation), endothelium-dependent hyperpolarizing factor (potassium-channel dependent relaxation) and endothelium-independent relaxation (nitroprusside). Contractions were tested to endothelium-dependent contracting factor (acetylcholine contraction with blocked relaxation); phenylephrine, U-46,619 and endothelin-1. Plasma L-arginine and asymmetric dimethylarginine were measured by high performance capillary electrophoresis. 13 RESULTS: The micro-arterioles from HIV positive women had significantly (% change in tension; P<0.05) reduced acetylcholine relaxation (-51 ± 6 vs. -78 ± 3%), endothelium-dependent relaxation factor (-28 ± 4 vs. -39 ± 3%), endothelium-dependent hyperpolarizing factor (-17 ± 4 vs. -37 ± 4%) and decreased nitric oxide activity (0.16 ± 0.03 vs. 0.70 ± 0.16 Δ unit) but unchanged nitroprusside relaxation. They had significantly enhanced endothelium-dependent contracting factor (+21 ± 6 vs. +7 ± 2%) and contractions to U-46,619 (+164 ± 10 vs. +117 ± 11%) and endothelin-1(+151 ± 12 vs. +97 ± 9%), but not to phenylephrine. There was enhanced reactive oxygen species with acetylcholine (0.11 ± 0.02 vs. 0.05 ± 0.01 Δ unit; P<0.05) and endothelin-1 (0.31 ± 0.06 vs. 0.10 ± 0.02 Δ unit; P<0.05). Plasma L-arginine: assymetric dimethyl arginine rates was reduced (173 ± 12 vs. 231 ± 6 μmol·μmol-1, P<0.05). 14 CONCLUSION: Premenopausal HIV positive womenhad microvascular oxidative stress with severe endothelial dysfunction and reduced nitric oxide and arginine: assymetric dimethylarginine ratio but enhanced endothelial, thromboxane and endothelin contractions. These microvascular changes may herald later cardiovascular disease.
Authors: Carlos Jericó; Hernando Knobel; Milagro Montero; María L Sorli; Ana Guelar; Juan L Gimeno; Pere Saballs; Jose L López-Colomés; Juan Pedro-Botet Journal: Am J Hypertens Date: 2005-11 Impact factor: 2.689
Authors: Jared M Baeten; Deborah Donnell; Patrick Ndase; Nelly R Mugo; James D Campbell; Jonathan Wangisi; Jordan W Tappero; Elizabeth A Bukusi; Craig R Cohen; Elly Katabira; Allan Ronald; Elioda Tumwesigye; Edwin Were; Kenneth H Fife; James Kiarie; Carey Farquhar; Grace John-Stewart; Aloysious Kakia; Josephine Odoyo; Akasiima Mucunguzi; Edith Nakku-Joloba; Rogers Twesigye; Kenneth Ngure; Cosmas Apaka; Harrison Tamooh; Fridah Gabona; Andrew Mujugira; Dana Panteleeff; Katherine K Thomas; Lara Kidoguchi; Meighan Krows; Jennifer Revall; Susan Morrison; Harald Haugen; Mira Emmanuel-Ogier; Lisa Ondrejcek; Robert W Coombs; Lisa Frenkel; Craig Hendrix; Namandjé N Bumpus; David Bangsberg; Jessica E Haberer; Wendy S Stevens; Jairam R Lingappa; Connie Celum Journal: N Engl J Med Date: 2012-07-11 Impact factor: 91.245
Authors: Samuel A Bozzette; Christopher F Ake; Henry K Tam; Sophia W Chang; Thomas A Louis Journal: N Engl J Med Date: 2003-02-20 Impact factor: 91.245
Authors: Nina Friis-Møller; Peter Reiss; Caroline A Sabin; Rainer Weber; Antonella d'Arminio Monforte; Wafaa El-Sadr; Rodolphe Thiébaut; Stephane De Wit; Ole Kirk; Eric Fontas; Matthew G Law; Andrew Phillips; Jens D Lundgren Journal: N Engl J Med Date: 2007-04-26 Impact factor: 91.245
Authors: Pragney Deme; Mohammed Moniruzzaman; David Moore; Robert Heaton; Ronald Ellis; Scott Letendre; Norman Haughey Journal: Neurology Date: 2022-07-18 Impact factor: 11.800