Siddhi Bhirud

Curriculum Vitae

Research Interests

Aortic valve stenosis (AVS)  is characterized by the stiffening of the valves, leading to altered mechanics of the leaflets. The main population of cells in a valve are the valvular interstitial cells (VICs). AVS can result in the activation of the VICs from quiescent fibroblasts to myofibroblasts and osteoblast-like cells. This results in the formation of aSMA stress fibers, increased deposition of extracellular matrix (ECM), and calcification. Recent studies have shown sexually dimorphic fibro-calcification as a result of AVS. AVS in males is seen as the calcification of the valve, whereas AVS in females is a gradual change from fibrosis to calcification.

AVS is also associated with chronic inflammation. VIC phenotype is primarily influenced by environmental cues, one such example is inflammatory signaling. Mice studies have shown that males with AVS show more pro-inflammatory M1 macrophages in the valve and females with AVS show more anti-inflammatory M2a macrophages. We would like to investigate more about the interplay between immune cells and VICs as AVS develops. With the use of a MMP degradable poly(ethylene-glycol) gel with a Collagen interpenetrating network to encapsulate our cells, we will study cell interactions and disease progression in a 3D system.