Rasheeda Mohd Zamin
Thesis: Arterial remodelling: The role of inflammatory factors (CX3CR1,CCR4 and RANK) in peripheral arterial disease
Medial calcification is a highly regulated process and it is also a significant feature of peripheral arterial disease (PAD). The calcification may arise from active remodelling process by osteoblast-like cells found in PAD and these cells may activate infiltrating monocytes and differentiate them into osteoclasts. Several inflammatory factors such as CX3CR1, CCR2 and RANK have been implicated in chronic arterial diseases involving coronary and carotid arteries.
This study aimed to characterize the morphology of arteries harvested from lower limbs amputated for PAD and investigate the phenotype and function of arterial smooth muscle cells (ASMC) derived from these samples. A total of 35 arteries obtained from PAD amputations (N=10) were compared with 40 control arteries obtained from cadavers (n=8) and non-PAD amputations (n=2). All arteries were cryo-processed without decalcification or dewaxing for standard histological staining with Hematoxylin and Eosin (H&E) and Oil red O’. Osteoclast activity was investigated with fluorescent tartrate resistant acid phosphatase (TRAP). Morphological changes in the artery were evaluated with scoring of medial calcification and lipid deposition. ASMC explanted from fresh PAD samples were characterized and compared with control ASMC (from fresh non-PAD samples).
Why my research is important
Vascular calcification has been a significant feature for peripheral arterial disease (PAD). Imaging modalities indicates tibial artery calcification as a significant indicator for future amputations. Similar to ectopic bone formation, arterial calcification may be seen as active remodelling which involves two key factors: osteoblasts and osteoclasts. Many studies have indicated that medial calcification may arise from trans-differentiation of arterial smooth muscle cells (ASMC) into osteoblast-like cells. However, the contribution of osteoclasts to arterial calcification in PAD is still not clear.