Vascular Complications.

Our mission is to understand fundamental mechanisms in molecular and cellular biology leading to cardiovascular diseases.

The end goal of our studies is to develop more effective treatments for the debilitating conditions associated with vascular complications.

What impact will this research have?

Understanding how cells are dysregulated in cardiovascular disease and related pathologies will help in the development of new therapeutics to combat disease and improve quality of life.

Current projects and goals

The Vascular Complications Group focuses on the development of atherosclerosis and cardiovascular disease (CVD), with particular emphasis on gene regulation and aberrant cell proliferation and cell death. We have identified a new player in the development of vascular disease; the role of TRAIL (TNF-related apoptosis-inducing ligand) in atherosclerosis and arterial thickening, both in vitro and in vivo using Trail-/- and Trail-/-Apoe-/- mice has already provided critical insights into cell survival and death, in the normal and diseased vessel wall, and opened up new opportunities for therapeutic intervention. Using unique models the Vascular Complications Group’s current research is focused on answering critical questions and exploring underlying mechanisms into vascular diseases, obesity, diabetes and kidney disease.

Investigating the role of Wnt signalling in vascular calcification and aging

This project seeks to investigate the potential of targeting the Wnt signalling pathway in medial vascular calcification. In particular, we aim to test whether Wnt signalling contributes to vascular calcification by regulating the expression of osteoprotegerin (OPG, an inhibitor of vascular calcification), receptor activator of nuclear factor-κB ligand (RANKL, an activator of osteoclastogenesis and vascular calcification) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL, modulator of RANKL expression) in vascular smooth muscle cells (VSMCs) in vitro, ex vivo and in vivo. We will also examine whether these pathway(s) are dysregulated in aging.

A range of techniques can be used in this study, including cell culture, molecular biology (e.g. luciferase assays, chromatin immunoprecipitation, electrophoretic mobility shift assays), PCR and Western blotting. Further interrogation will involve ex vivo aortic calcification experiments and in vivo models of vascular calcification. 

Is activation of the FasL/Fas pathway harmful or advantageous in atherosclerosis?

In this study, we will interrogate the role of the FasL/Fas pathway in atherosclerosis-prone lab models, as well as investigate circulating levels in patients with coronary artery disease. This proposal has significant implications for understanding FasL signalling in the vasculature in vivo, but also in people with cardiovascular disease. Comprehension of these signalling pathways may lead to novel approaches in the prevention and/or treatment of the significant morbidity and mortality associated with atherosclerosis.

A range of techniques can be used in this study, including cell culture and molecular biology techniques (e.g., luciferase assays, chromatin immunoprecipitation, electrophoretic mobility shift assays), gene expression (PCR, Western blotting), ELISA, and in vivo models of atherosclerosis. 

Identify the role of endothelial and vascular smooth muscle cell cross-talk in blood vessel development 

Angiogenesis is the growth of capillary networks consisting of endothelial cell (EC) tubes, driven by hypoxia-induced mediators, the most characterised being vascular endothelial growth factor (VEGF). Remodelling, maturation and stabilisation of existing vessels by perivascular cells (pericytes in capillaries, or vascular smooth muscle cells (VSMCs) in larger vessels) are essential for generating functional collateral vessel networks in ischaemia. This proposal extends on our published findings showing TNF-related apoptosis-inducing ligand (TRAIL) as a new molecule critical in generating stable blood vessels by simultaneously stimulating angiogenesis, vessel stability and remodeling. How TRAIL does this is not fully established, and the cross-talk between EC and VSMCs in TRAIL-dependent blood vessel generation is unknown.

Using world-first EC and VSMC-specific Trail-/- lab models, we will identify the contribution of TRAIL coming from each cell type to blood vessel development in vivo using cutting edge technology and imaging. This work will determine how crucial TRAIL-dependent EC and VSMC cell-cell contact is crucial for vessel formation.

A range of techniques can be used in this study, including the in vivo Matrigel plug assay, histology, CT scanning, gene expression (PCR, Western blotting) and ELISA. 

Dr Mary Kavurma
Research group led by:
Research covers areas of:
Latest news

Neutrophils in acute coronary syndrome

HRI researchers Dr Rahul Kurup and Associate Professor Sanjay Patel from the Cell Therapeutics Group recently published a review of the role of neutrophils in acute coronary syndrome. With abundant data demonstrating this role, this presents opportunities to develop novel diagnostic and prognostic biomarkers and therapeutic agents that specifically target neutrophils.
Current team update

Dr Siân Cartland has been awarded a Sydney Medical School Early Career Research Grant.

Sep 08, 2015

Awards and Achievements 

Dr Belinda Di Bartolo:

Sydney Medical School Early Career Research Grant 2015

Finalist for the Junior Investigator Award for Women for ATVB May 2015

Presented in the ATVB Young Investigator session at the American Heart Association Meeting Chicago, Nov 2014

Dr Siân Cartland

Sydney Medical School Early Career Research Grant 2015

Awarded a HRI Award 2014

Ian Potter Foundation Travel Award 2013

Australian Vascular Biology Society Travel Award 2013

Presented with an Exceptional Abstract Award at the International Vascular Biology Society Meeting Japan 2013

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