Wei Chao, MD, PhD
Associate Professor, Harvard Medical School
Anesthesia for General Surgery, Orthopedic Surgery, and Obstetrics
TLR Signaling in Ischemic Myocardial Injury
Signaling via Toll-like receptors (TLRs) is a critical component of innate immune system and represents the first line of host defense against microbial infection. Through the "molecular pattern-recognition," TLRs recognize invading pathogens, transduce the signals via distinct intracellular pathways involving adaptor proteins such as MyD88 and Trif, and ultimately lead to inflammatory responses. In addition, recent studies have suggested that TLRs may also play an important role in tissue injury due to non-infectious insults such as myocardial ischemia. The goal of this project is to determine the role of distinct TLR signaling pathways in the development of ischemic myocardial injury and the underlying mechanisms that control the effects.
TLRs in Cardiac Dysfunction During Polymicrobial Sepsis
Sepsis has a prevalence of 750,000 cases each year. In severe cases such as septic shock, the mortality reaches as high as more than 40%. During sepsis, components of microorganisms interact with host immune system and induce a profound systemic inflammatory response clinically manifested as a hypotension, poor tissue perfusion, and organ dysfunction. Cardiac dysfunction represents a main feature of severe sepsis and contributes to its high mortality. Yet, our understanding of the signaling mechanisms controlling this critical event remains incomplete. The goal of this project is to define the role of TLR signaling in the pathogenesis of sepsis. Using a mouse model of polymicrobial peritonitis sepsis and a variety of genetically modified mouse strains, we test the contribution of a specific TLR signaling to the development of septic injury such as cardiac dysfunction and mortality. Various techniques have been established in the lab to measure myocardial dysfunction during sepsis, including serial echocardiography in vivo, isolated hearts perfused in Langendorff system, and sarcomere shortening and intracellular Ca2+ transients in single cardiomyocytes.
Hunan Medical University, MD
University of Texas, PhD
Featured Publication (Full Text)
Toll-like receptor signaling: a critical modulator of cell survival and ischemic injury in the heart, Am J Physiol Heart Circ Physiol. 2009 Jan;296(1):H1-12. Epub 2008 Nov 14.
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Cardiac Critical Care Research Program
Department of Anesthesia, Critical Care and Pain Medicine
55 Fruit Street
Boston, MA 02114