Date of Award
12-2023
Degree Type
Thesis
First Advisor
Dr. Muhammad Zuhair Yusuf
Second Advisor
Dr. Hasan Salman Siddiqui
Third Advisor
Dr. Mati-Ur-Rehman
Department
Biological and Biomedical Sciences
Abstract
Background: Type 2 Diabetes Mellitus (T2DM) is a heterogeneous metabolic disorder with complex pathogenesis. It is highlighted by hyperglycemia, oxidative stress, and inflammatory profile that entails endothelial dysfunction and vascular inflammation thereby impacting multiple body organs. These inflammatory engagements and imbalances between vasodilators impact platelet activity and lead to macrovascular and microvascular thrombotic complications. The endothelial mediators - prostacyclin (PGI2) and nitric oxide (NO), keep the thrombogenic status of an individual under check by impacting the actin cytoskeletal framework of platelets and endothelium, along with implications on vascular diameter. When platelets are activated, their underlying actin cytoskeleton is remodelled, changing their shape and allowing the release of mediators from platelets. The process of rearrangement is intricate and well-coordinated, influencing the development of stress fibers, actin nodules, lamellipodia, and filopodia. The formation of stress fibres illustrates a fully activated platelet while the presence of actin nodules marks their pre-fully activated form. The beneficial role of prostacyclin on platelet and endothelial front has been under consideration to control thrombus formation via inhibition of platelets and to restore the effect of endothelial mediators in the circulation. The disease under consideration is T2DM which has underlying thrombotic pathogenesis for its complications. Aims: Iloprost, a long-acting PGI2 analogue can mediate platelet activity that would generate an impact on the diabetic pathogenesis and its vascular complications.
Methodology: Platelets from the healthy and diabetic participants were assessed for their spreading profiles in an in-vitro setting. The effect of iloprost on impacting platelets in circulation and in a formed clot were assessed by dose and time course assays. To identify a platelet-specific response and not impact vascular dilatation, a drug-induced rat model of type 2 diabetes mellitus was established and assessed for its dilatation of aorta.
Result and Discussion: Our results indicate T2DM to have increased platelet activity which was reduced by iloprost in both dose response and time-dependent manner. Interestingly, T2DM required higher doses of iloprost to generate a similar effect but these doses still were lower to impact on vascular dilatation.
Conclusion: This effect was seen to effectively translate iloprost use in emergency and preventive thrombotic implications in T2DM patients.
First Page
1
Last Page
51
Recommended Citation
Nasir, S. P.
(2023). Role of prostacyclin analogue in curbing thrombotic complications of type 2 diabetes mellitus. , 1-51.
Available at:
https://ecommons.aku.edu/etd_pk_mc_mphil-bbs/25