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Function of Vascular Endothelial Cells in Aging and Hypothermia: Clinical Implications

Osama, Mohammad
http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1534939514503588

Abstract Details

2018, Doctor of Philosophy (PhD), Ohio University, Chemistry and Biochemistry (Arts and Sciences).
Advancing age is the primary risk factor for cardiovascular, cerebrovascular and renal diseases. The imbalance between prooxidative and antioxidative processes increase with senescence. The decrease in cytoprotective nitric oxide (NO) and increase in reactive oxygen species (ROS) such as superoxide (O2¯) and peroxynitrite (ONOO¯) are suggested to be the main factors of endothelial dysfunction and aging. Endothelial dysfunction is associated with the impaired generation of NO and overproduction of O2¯ resulting in the formation of cytotoxic ONOO¯. Replicative senescence of human endothelial cells (ECs) was analyzed here using human umbilical vein endothelial cells (HUVECs). In this study, we employed a nanomedical system to measure the concentration of NO, O2¯, and ONOO¯ simultaneously. Peroxynitrite is a powerful cytotoxic oxidant formed from the reaction between NO and O2¯. Nanosensors were placed near the endothelium and calcium ionophore-stimulated NO, O2¯, and ONOO¯ were measured. The present work was performed to investigate endothelial nitric oxide synthase (eNOS) dysfunction during aging of endothelial cells. The age-related cardiovascular diseases such as heart failure, atherosclerosis, ischemic heart disease and myocardial infarction can be associated with endothelial dysfunction. The nanomedical approach enabled us to characterize changes in eNOS coupling/uncoupling as a function of biological aging. The release of NO and ONOO¯ was studied in different passages in ethnic groups (Caucasian Americans (CAs), African Americans (AAs) and Asian Americans (ASAs)). Our results suggest that HUVECs of AAs are more susceptible to endothelial dysfunction during aging. The shortening of relative telomere length in aging coincided with a decrease of NO and increase of ONOO¯ concentrations. The imbalance between [NO] and [ONOO¯] was due to endothelial dysfunction. The treatment of aging endothelium with factors affecting the eNOS pathway (e.g., VAS2870, PEG-SOD, and L-arginine) partially restored [NO]/[ONOO¯] balance in aging-induced senescent endothelial cells. The beneficial effects of these factors on aging endothelial function were clearly associated with a decrease in the overexpressed eNOS, iNOS, and NADPH oxidase 4 functions with aging in all races. The treated HUVECs improved eNOS coupling and restored endothelial function in aging. This novel study demonstrates that the imbalance between [NO] and [ONOO¯] increases with aging. This finding may be clinically exploited to prevent the effect of age-induced cardiovascular disease using a compensatory defense strategy. Therapeutic hypothermia (TH) is an accepted clinical procedure used during vascular surgery. We explored an association between TH and function in human umbilical vein endothelial cells (HUVECs). The HUVECs were subjected to hypothermia and normothermia. The concentrations of NO, O2¯, and ONOO¯ were measured using nanosensors. We showed that the TH increases [NO]/[ONOO¯] to improve endothelial function in control (untreated), dysfunctional and L-arginine treated HUVECs of CAs, AAs, and ASAs. We also demonstrated that TH is essential for preserving physiological [NO]/[ONOO¯] balance and can prevent endothelial damage during vascular surgery.
Tadeusz Malinski, PhD (Advisor)
175 p.
Aging; Alternative Medicine; Cellular Biology; Chemistry; Developmental Biology; Endocrinology; Environmental Science; Environmental Studies; Epidemiology; Health Care; Health Sciences; Immunology; Medicine; Microbiology; Molecular Biology; Molecular Chemistry; Molecules; Nanoscience; Nanotechnology; Neurobiology; Neurology; Neurosciences; Oncology; Organic Chemistry; Organismal Biology; Pharmaceuticals; Pharmacology; Pharmacy Sciences; Physiology; Polymer Chemistry; Sports Medicine; Therapy; Toxicology; Zoology
Aging, Therapeutic hypothermia; Caucasian Americans; African Americans; Asian Americans; Endothelial nitric oxide synthase; NADPH ox; Human umbilical vein endothelial cells; VAS2870; PEG-SOD; L-arginine; Angiotensin II; L-arginine; Clinical implications

Recommended Citations

Citations

  • Osama, M. (2018). Function of Vascular Endothelial Cells in Aging and Hypothermia: Clinical Implications [Doctoral dissertation, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1534939514503588

    APA Style (7th edition)

  • Osama, Mohammad. Function of Vascular Endothelial Cells in Aging and Hypothermia: Clinical Implications. 2018. Ohio University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1534939514503588.

    MLA Style (8th edition)

  • Osama, Mohammad. "Function of Vascular Endothelial Cells in Aging and Hypothermia: Clinical Implications." Doctoral dissertation, Ohio University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1534939514503588

    Chicago Manual of Style (17th edition)

ohiou1534939514503588
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This open access ETD is published by Ohio University and OhioLINK.