NSF funds Agarwal’s study of collagen abnormalities in aortic aneurysms
Calcification of soft tissues is a hallmark of several cardiovascular diseases like aortic aneurysms, atherosclerosis and calcific aortic valve disease. Calcification is often preceded by extensive remodeling of the extracellular matrix (ECM) in the underlying tissue.
While the structural changes and role of elastin in the ECM are well characterized in cardiovascular diseases, much less is understood about collagen, the most abundant ECM protein in the human body. Collagen fibrils provide strength, elasticity and mechanical stability to the body.
Agarwal is partnering with Dr. Michael Go, an associate professor of vascular surgery at the College of Medicine, to examine collagen fibrils in vascular diseases. The team’s recent research has demonstrated how structurally altered, or abnormal, collagen fibrils exist in abdominal aortic aneurysm (AAA), a life-threatening vascular disease.
For this NSF award, the team will test the overall hypothesis that abnormal collagen fibrils in AAA serve as the major substrates for calcific deposits due to irregularities in their surface-charge distribution. Studies will be conducted at the single fibril level on human AAA tissue, by mapping the surface charge and nanoscale calcific deposits using atomic force microscopy (AFM) and electron microscopy approaches. The proposed efforts will be accomplished through a Bruker Resolve AFM recently acquired by Agarwal as shared equipment via a NIH S10 award (S10OD025096). The research supported by this grant will also provide multidisciplinary hands-on research experience to graduate and undergraduate students and enrichment activities to underserved K-8 students.
The insights gained from this work may help improve cardiovascular outcomes by influencing new strategies for early diagnosis and treatment and aiding development of cardiovascular bioprostheses.