Platelet and endothelial function : Polycystic Ovary Syndrome and the renin-angiotensin system.
Date
2009
Authors
Rajendran, Sharmalar
Editors
Advisors
Horowitz, John David
Chirkov, Yuliy
Willoughby, Scott Richard
Chirkov, Yuliy
Willoughby, Scott Richard
Journal Title
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Thesis
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Abstract
The phenomenon of platelet hyperaggregability and decreased platelet
responsiveness to nitric oxide (also termed as nitric oxide resistance),
documented in several cardiovascular disease states, is associated with
adverse cardiovascular outcomes.
The series of experiments described in this thesis address primarily some
aspects of the pathophysiology, epidemiology and therapy of the phenomenon
of end-organ resistance to nitric oxide (NO) in two important conditions, that
are closely associated with cardiovascular risk factors and disease states:-
Polycystic ovary syndrome, which is closely linked with the metabolic
syndrome and premature subclinical atherosclerosis.
The renin-angiotensin system, which is recognized as a significant mediator
in the pathophysiology of a number of cardiovascular disease states.
The first study examined the epidemiology/pathophysiology of putative
platelet/endothelial dysfunction in young individuals with PCOS. The
subsequent studies focused on the potential impact of the renin-angiotensin
system on platelet and endothelial function. This mechanistic review is set in
the context of a number of recent major clinical studies which have
demonstrated surprising efficacy of certain angiotensin-converting enzyme
(ACE) inhibitors (ramipril and perindopril) in the prevention of thrombotic
processes. Thus we tested the hypothesis whether ACE inhibitor ramipril
sensitizes platelets to NO (as a potential mechanism for improved
cardiovascular outcomes) in a high risk patient cohort. In addition, particular
attention will be given to the emerging role of the heptapeptide Angiotensin-
(1-7), a possible physiological antagonist to Angiotensin II in the vasculature
and the limitation of the current literature concerning potential effects of the
renin-angiotensin system on thrombotic mechanisms.
School/Discipline
School of Medicine
Dissertation Note
Thesis (Ph.D.) - University of Adelaide, School of Medicine, 2009
Provenance
Copyright material removed from digital thesis. See print copy in University of Adelaide Library for full text.