Mark Entman Lab

Our lab is devoted to the study of cellular and molecular mechanisms associated with cardiovascular function and mechanisms of cardiovascular injury and aging.

We also provide technology transfer, instrumentation services, collaborative advice and facilities to enhance cardiovascular research through our Animal Core.

Dr. Mark Entman is the chief of the Division of Cardiovascular Sciences

Cellular and Molecular Basis of Cardiac Repair

Mark L. Entman, Katarzyna A. Cieslik, JoAnn Trial

We are interested in the cellular and molecular responses to the loss of homeostasis in the heart. This loss could include chronic injury or aging. The cells responsible for repair are mainly fibroblasts, and the molecular basis for their responses includes signaling through the cytokines TGF-β and interleukin 6 as well as mechanosensing via integrins connecting them to the extracellular matrix. The response of fibroblasts to these signals changes with age, such that they are less capable of producing a mature scar upon loss of cardiac myocytes, and more likely to produce interstitial fibrosis. We are investigating the cause of this as a relative loss of responsiveness to TGF-β (via internal signaling components) and an alteration of the matrix produced and thus a change in mechanosensing.

Inflammation in Cardiovascular Injury and Remodeling

Mark L. Entman, JoAnn Trial, Katarzyna A. Cieslik

Damage to the heart induces an inflammatory response from circulating blood leukocytes. These cells enter the heart and can establish either a pro-inflammatory or a pro-fibrotic environment depending on the stage of the response. The environment informs fibroblasts to respond by migrating, proliferating, and producing extracellular matrix. The leukocytes can also, in conjunction with the fibroblasts, break down components of the matrix as well as continuing to maintain it. We are investigating the nature of the inflammatory response in young versus old animals, as well as how these cells work with fibroblasts to heal or remodel the tissue.

Cellular Pathophysiology in the Aging Heart

Katarzyna A. Cieslik, JoAnn Trial, Mark L. Entman

We are exploring both the active and passive components of diastolic dysfunction in aging. The increased fibrosis leads to a stiffer ventricle impairing LV filling and inducing left atrial enlargement. We are studying the inflammatory pathways that seem to be key contributors to the increase in fibrosis. We are also studying the active, cardiomyocyte dependent, diastolic dysfunction in aging using interventions that modify mitochondrial function.

Whole Animal Instrumentation and Monitoring

George E. Taffet, Anilkumar K. Reddy

We are using telemetry-based probes to study cardiovascular function in situ in the mouse and plan to study aging with serial measurements in the same mouse as it ages. One probe can assess stroke distance and peak aortic flow velocity by Doppler. In addition to heart rate and temperature, our probes also measure activity so we can assess gait speed and physical function. This is a collaboration with Indus Instruments.

Aortic Impedance and Vascular Mechanics

George E. Taffet, Anilkumar K. Reddy

Aortic Impedance and Vascular Mechanics George E. Taffet, Anilkumar K. Reddy Using a combination of invasive and non-invasive measurements we are interested in studying the large artery function in the mouse. We use pulse wave velocity and aortic impedance to assess vascular function in anesthetized mice.