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JACC March 24, 2020

Volume 75, Issue 11

Vascular Medicine
IMPAIRED SOD2 ACTIVITY LINKED WITH EXCESSIVE MITOCHONDRIAL SUPEROXIDE IS
RESPONSIBLE FOR DIMINISHED RE-ENDOTHELIALIZATION OF ENDOTHELIAL PROGENITOR CELLS
IN HYPERTENSION
Poster Contributions
Posters Hall_Hall A
Saturday, March 28, 2020, 3:45 p.m.-4:30 p.m.

Session Title: Vascular Medicine: Basic 3

Abstract Category: 38. Vascular Medicine: Basic
Presentation Number: 1212-202

Authors: Jiang He, Gaoxing Zhang, Xing Liu, Bingbo Yu, Xinzhu Tong, Yijia Shao, Jiapan Sun, Jun Tao, The First Affiliated Hospital of Sun
Yat-sen University, Guangzhou, People’s Republic of China, Jiangmen Central Hospital of Sun Yat-sen University, Jiangmen, People’s
Republic of China
Background: Dysfunction of endothelial progenitor cells (EPCs) give rise to deficient endothelial reparative capacity in patients with
hypertension; however the mechanisms remain poorly defined. Mitochondrial superoxide (mtSO) is implicated in the pathogenesis of
endothelial injury in hypertension. Acetylation of SOD2 is vital for scavenging mtSO. Our present study aim to investigate the role of mtSO
in regulating reendothelialization of EPCs and identify SOD2 deacetylation as a novel endothelial protective mechanism in hypertension.
Methods: Thirty hypertensive patients and 30 age-matched healthy subjects were enrolled. Reendothelialization capacity of EPCs were
examined in carotid artery injury nude mice. MtSO were detected by MitoSOX. HPLC and western blot were used to measure acetylation of
SOD2. We evaluated the impact of deacetylation of SOD2 on mtSO and reendothelialization capacity of EPCs.
Results: EPCs from hypertensive patients displayed excessive mtSO and oxidative damage, including loss of membrane potential,
abnormal ultrastructure, and mtDNA injury, which was coincided with impaired reendothelialization capacity. Scavenging of mtSO with
SOD2 mimic, mitoTEMPO, inhibited mitochondrial oxidative damage and rescued EPC function. Enzymatic activity and deacetylation
of SOD2 were reduced in hypertension. Administration of nicotinamide, a deacetylases inhibitor, increased acetylation at K68 of SOD2
in a time-dependent manner, thereby inducing oxidative damage and impaired EPC function. SOD2 K68 deacetylation mimic mutant
(SOD2K68Mut) were made by substitution of a lysine with an arginine mimics deacetylation. Adv-SOD2K68Mut was transfected into EPCs.
SOD2K68Mut-EPCs presented remarkedly reduced acetylation level and enhanced activity of SOD2. Suppression of SOD2 acetylation
dramatically eliminated mtSO and improved reendothelialization capacity of EPCs.
Conclusion: The present study demonstrated for the first time that elevated mtSO production due to hyperacetylation of SOD2 contributes
to deficient reendothelialization capacity of EPCs in hypertension. Suppression of SOD2 acetylation may be a novel therapeutic target for
endothelial injury.

Descargado para LORE HOYOS (leidylambertinez@unisinu.edu.co) en University of Sinu de ClinicalKey.es por Elsevier en abril 06, 2021. Para
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