Connect Issues Winter 2021

p Michael Samaan, PhD, University of Kentucky studies muscle-based interventions that may lead to reduction in hip joint pain and cartilage degeneration within the Marfan population.

VEDS Research David Shreiber, PhD, Rutgers University The structure-function effects of specific collagen-III mutations in VEDS

VEDS is caused by mutations in collagen-III, a major structural component of the extracellular matrix (ECM) that provides strength and structure to blood vessels and other elastic tissues. The research goal is to understand how specific mutations in collagen-III lead to altered blood vessel structure and/ or cell behavior in VEDS. By studying how the mutations in collagen-III affects blood vessel strength, the researchers hope to understand the impact of specific mutations on the severity of VEDS and open new therapeutic avenues for people with VEDS, including potential targets for gene editing. Orthopedics for Marfan Michael Samaan, PhD, University of Kentucky Hip joint function and health in patients with Marfan syndrome Approximately 46% of people with Marfan syndrome self-report hip joint pain. A diagnostic feature of Marfan syndrome is acetabular protrusion, which leads to a higher risk of developing secondary hip osteoarthritis. This study will use a novel multi-modality approach consisting of gait analysis, musculoskeletal simulations, and magnetic resonance imaging to assess differences in hip abductor strength, abductor morphology (volume and fatty infiltration), and hip joint contact forces (JCF) in people with Marfan syndrome and healthy controls. The researchers will also determine the ability of hip joint abductor muscle volume, hip abductor fatty infiltration, and hip JCF to predict severity of hip joint pain and hip joint cartilage degeneration within the Marfan population. This study is the first to mechanistically assess the effects of Marfan on hip joint muscle function and joint mechanics that may be involved in development of hip osteoarthritis in this population. The results of this study will provide insight into the development of targeted muscle-based interventions that will reduce hip joint pain and hip joint cartilage degeneration within the Marfan population. Early Investigator Award Anna Cantalupo, PhD, Icahn School of Medicine at Mount Sinai A new druggable epigenetic pathway in Marfan syndrome Using an innovative research strategy, the researchers have used a validated mouse model of Marfan syndrome to link TAAD (thoracic aortic aneurysms and dissections) development with increased activity of an enzyme called Hipk2. Both human and mouse aortas express Hipk2 and both people and mice with Marfan have increased amounts of Hipk2 in their aortas. Importantly, the researchers have also reported that Marfan mice with genetic inactivation of Hipk2 fail to develop TAAD, suggesting that they could prevent TAAD progression by blocking the way Hipk2 works in the body. In this study the researchers hope to identify new factors of TAAD in Marfan syndrome that can be blocked collectively or separately using drugs that are already approved or can be defined. Together, these animal studies will provide evidence- based support for testing new compounds in clinical trials involving people with TAAD.

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Winter 2021