Evaluation of plant-derived compounds as novel therapies for vascular calcification

Entry requirements

Please use this Research Proposal, Personal statement and CV writing guide when preparing an application.

Months of entry

Anytime

Course content

About the Project

Atherosclerosis is a progressive vascular disease initiated by endothelial dysfunction. It is characterised by the infiltration of low-density lipoproteins (LDLs) into the subendothelial spaces, where they accumulate and become modified, predominantly by oxidation. Oxidised-LDL activates endothelial cells to secrete inflammatory mediators and to express high levels of adhesion molecules that attract circulating monocytes to the sub-endothelial space, leading to the formation of atheromatous plaques within the arterial wall. As these plaques grow, the risk of rupture and subsequent cardiovascular events highly depends on plaque composition - which includes the extent of plaque calcification (Kawai et al., 2024). Intimal calcification is the formation of mineralised tissue within atherosclerotic plaques, and it is largely driven by the oxidative and pro-inflammatory environment which exists in these plaques (Mitsis et al., 2024). Currently, no anti-calcific treatments exist.

Historically, plant-derived compounds (phytochemicals) have been used in traditional Chinese and Indian medicinal practices, but they have now been highlighted to possess a wide range of therapeutic potential in cardiovascular disease (Waltenberger et al., 2016). Notably, Asiaticoside is a triterpene glycoside derived from the plant Centella asiatica, and Asiaticoside has been reported to have both anti-inflammatory and anti-oxidant effects (Bandopadhyay et al., 2023).

Aims & Objectives

Preliminary investigations within our research group have shown that Asiaticoside inhibits the deposition of a mineralised matrix by vascular smooth muscle cells in vitro. Based on these findings, the proposed PhD project would seek to:

1) Further evaluate Asiaticoside and other natural compounds derived from plants for their potential as novel anti-calcific agents.

2) Characterise the molecular mechanisms which underpin the activity of plant-derived compounds observed in our preliminary investigations.

Methods

In this project the student will gain a wide range of laboratory skills, including cell culture methods to study the effects of natural compounds on vascular smooth muscle cell calcification in vitro and ex vivo, biochemical and molecular approaches to quantify cytokine production (ELISA), and changes in gene and protein expression (RT-PCR, western, immunofluorescence).

How to apply

For more information about this project please contact Dr Samanta Borland: s.borland@salford.ac.uk

Fees and funding

This programme is self-funded.

To enquire about University of Salford funding schemes – including the Widening Participation Scholarship – visit this website