Tryfonos, A (2020) THE IMPACT OF ARTERIAL CATHETERIZATION ON VASCULAR FUNCTION IN HEALTHY SUBJECTS AND PATIENTS WITH CORONARY ARTERY DISEASE. Doctoral thesis, Liverpool John Moores University.

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Abstract

Coronary artery disease (CAD) is the leading cause of global death. Diagnosis and treatment for CAD often involves angiography and/or angioplasty. However, the radial artery catheterization required during both procedures may result in acute artery dysfunction/damage, mainly due to endothelial disruption. Whilst exercise training typically enhances endothelial function, and is therefore generally recommended for CAD patients, animal studies indicated paradoxical exercise-induced vasoconstriction post-catheterization. It is not currently known if there is an acute period when exercise is detrimental due to catheter-induced damage. Chapter 4 has demonstrated that catheterization in CAD patients results in impaired flow-mediated dilation (FMD), but that arterial responses to handgrip exercise (HE) are preserved 1 week post-catheterization. This finding suggests that the impact of endothelial disruption may be stimulus specific, with redundant mechanisms likely to preserve exercise-mediated vasodilator responses in the face of catheterization-mediated damage. Chapter 6 showed that catheterization in young healthy males with a fully functional endothelium resulted in reduced FMD, including completely abolished FMD (≤0%) in approximately 1/5th of participants. This exaggerated response in healthy subjects, compared to CAD patients, raises the question of whether individuals with a priori endothelial dysfunction are more or less susceptible to catheterization-induced arterial risk. Given the association between endothelial dysfunction and CAD progression, Chapter 5 explored relationships between FMD and arterial responses to exercise with the protein content of eNOS, NAD(P)Hox subunit 2, NFκB, ET-1, nitrotyrosine, the senescence markers (p53, p21, p16) and eNOS Ser1177 phosphorylation in endothelial cells (EC)s obtained from the radial arteries of CAD patients. FMD was positively associated with eNOS Ser1177 phosphorylation, and protein content of p21 and p16, whereas no associations were found between FMD and markers of oxidative stress, vasoconstriction or inflammation. HE-induced dilation was not associated with any of the EC proteins, or FMD. A number of associations were observed between the expression of atherogenic risk-modulating proteins, providing novel insight into the molecular mechanisms related to vascular function in CAD. Lastly, Chapter 7 provided novel molecular insights into how elevated shear stress induced by exercise benefits endothelial function in humans. In particular, it has been shown that a ~5-fold increase in shear stress induced by 30 minutes of HE resulted in upregulation of eNOS Ser1177 phosphorylation, whereas no effect was reported in PECAM-1 Tyr713 activation in ECs obtained from radial artery of young healthy well-trained males. As such, this study suggests that PECAM-1 activation is not involved in the vascular response to prolonged elevations in shear stress. In conclusion, this thesis provided important information regarding the impact of catheterization on arterial function, showing preserved exercise-induced dilation in CAD patients following catheterization damage. This suggests early onset of exercise-based rehabilitation after catheterization procedures is safe, although this should be confirmed in other cohorts and in a larger sample. In addition, this thesis demonstrated novel insights into the molecular mechanisms related to arterial function in CAD, suggesting that progressive endothelial dysfunction in CAD may be more dependent on NO production than NO scavenging. Finally, this thesis provided novel data regarding the mechanism by which ECs sense elevated shear stress, suggesting no involvement of PECAM-1 in exercise-induced NO production.

Item Type:	Thesis (Doctoral)
Uncontrolled Keywords:	endothelial function; coronary artery disease; endothelial cell biopsy; catheterization
Subjects:	Q Science > QM Human anatomy Q Science > QP Physiology R Medicine > RC Internal medicine > RC1200 Sports Medicine
Divisions:	Sport & Exercise Sciences
Date Deposited:	23 Jun 2020 10:01
Last Modified:	05 Oct 2022 11:15
DOI or ID number:	10.24377/LJMU.t.00013129
Supervisors:	Dawson, E, Cocks, M and Green, D
URI:	https://researchonline.ljmu.ac.uk/id/eprint/13129

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