Original ArticlePharmacologic Inhibition of Myeloid Differentiation Factor 88 (MyD88) Prevents Left Ventricular Dilation and Hypertrophy After Experimental Acute Myocardial Infarction in the MouseVan Tassell, Benjamin W PharmD*‡; Seropian, Ignacio M MD*‡; Toldo, Stefano PhD†‡; Salloum, Fadi N PhD†; Smithson, Lisa BS‡; Varma, Amit MD†; Hoke, Nicholas N BS†; Gelwix, Christopher MD†; Chau, Vinh BS†; Abbate, Antonio MD, PhD†‡Author Information From the *School of Pharmacy, †VCU Pauley Heart Center, and ‡VCU Victoria Johnson Center, Virginia Commonwealth University, Richmond, VA. Received for publication October 28, 2009; accepted December 29, 2009. Supported by an A. D. Williams Research Grant to Dr Van Tassell and an American Heart Association Beginning Grant-in-Aid to Dr Abbate. Disclosures: None. The authors reports no conflicts of interest. Reprints: Benjamin W. Van Tassell, PharmD, Assistant Professor of Pharmacy, Virginia Commonwealth University, 410 North 12th Street, Rm 454A, Richmond, VA 23298 (e-mail: email@example.com). Journal of Cardiovascular Pharmacology: April 2010 - Volume 55 - Issue 4 - p 385-390 doi: 10.1097/FJC.0b013e3181d3da24 Buy Metrics Abstract Background: Myeloid differentiation factor 88 (MyD88) is an endogenous adaptor protein that coordinates the inflammatory response to agonists of the Toll-like receptor and interleukin-1 receptor families. This particular response is activated following myocardial ischemia and infarction and may represent a viable target for pharmacologic inhibition. The current study tested MyD88 inhibitors in a murine model of nonreperfused acute myocardial infarction (AMI). Methods: AMI was induced by permanent ligation of the left coronary artery. Adult, male, Imprinting Control Region mice were randomized to daily injections with 1 of 2 MyD88 pharmacologic inhibitors (ST2825 25 mg/kg or IMG2005 1 mg/kg), saline, or pretreatment with MyD88-targeted silencing small interfering RNA (siRNA) or scrambled nontargeted siRNA (n = 6 for each group). Echocardiography was performed at baseline and 7 days after surgery to evaluate pathologic cardiac enlargement. Results: Pharmacologic inhibition of MyD88 with ST2825 or IMG2005) and MyD88-targeted siRNA protected against left ventricular (LV) dilatation (reduced LV end-systolic and LV end-diastolic diameter) and hypertrophy. This protection occurred despite no measurable reduction in infarct size. Conclusions: Pharmacologic MyD88 inhibition protects against pathologic LV remodeling without altering infarct scar formation. MyD88 may be a viable target for pharmacologic inhibition in AMI. © 2010 Lippincott Williams & Wilkins, Inc.