Low-Density Lipoprotein Receptor–Related Protein-1 Is a Therapeutic Target in Acute Myocardial Infarction

• Main Authors: Stefano Toldo, PhD, Dana Austin, MS, Adolfo G. Mauro, MS, Eleonora Mezzaroma, PhD, Benjamin W. Van Tassell, PharmD, Carlo Marchetti, PhD, Salvatore Carbone, MS, Soren Mogelsvang, PhD, Cohava Gelber, PhD, Antonio Abbate, MD, PhD
• Format: Article
• Language: English
• Published: Elsevier 2017-10-01
• Series: JACC: Basic to Translational Science
• Subjects: ischemia reperfusion; low-density lipoprotein receptor-related protein-1; serine protease inhibitor; SERPINs
• Online Access: http://www.sciencedirect.com/science/article/pii/S2452302X17302024
• ISSN: 2452-302X

Low-density lipoprotein receptor–related protein-1 (LRP1) is a ubiquitous membrane receptor functioning as a scavenger and regulatory receptor, inducing anti-inflammatory and prosurvival signals. Based on the known structure–activity of the LRP1 receptor binding site, the authors synthesized a small peptide (SP16). SP16 induced a >50% reduction in infarct size (p < 0.001) and preservation of left ventricular systolic function (p < 0.001), and treatment with an LRP1 blocking antibody eliminated the protective effects of SP16. In conclusion, LRP1 activation with SP16 given within 30 min of reperfusion during experimental acute myocardial infarction leads to a cardioprotective signal reducing infarct size and preservation of cardiac systolic function.