The small molecule Chicago Sky Blue promotes heart repair following myocardial infarction in mice.

Journal Article (Journal Article)

The adult mammalian heart regenerates poorly after injury and, as a result, ischemic heart diseases are among the leading causes of death worldwide. The recovery of the injured heart is dependent on orchestrated repair processes including inflammation, fibrosis, cardiomyocyte survival, proliferation, and contraction properties that could be modulated in patients. In this work we designed an automated high-throughput screening system for small molecules that induce cardiomyocyte proliferation in vitro and identified the small molecule Chicago Sky Blue 6B (CSB). Following induced myocardial infarction, CSB treatment reduced scar size and improved heart function of adult mice. Mechanistically, we show that although initially identified using in vitro screening for cardiomyocyte proliferation, in the adult mouse CSB promotes heart repair through (i) inhibition of CaMKII signaling, which improves cardiomyocyte contractility; and (ii) inhibition of neutrophil and macrophage activation, which attenuates the acute inflammatory response, thereby contributing to reduced scarring. In summary, we identified CSB as a potential therapeutic agent that enhances cardiac repair and function by suppressing postinjury detrimental processes, with no evidence for cardiomyocyte renewal.

Full Text

Duke Authors

Cited Authors

  • Yifa, O; Weisinger, K; Bassat, E; Li, H; Kain, D; Barr, H; Kozer, N; Genzelinakh, A; Rajchman, D; Eigler, T; Umansky, KB; Lendengolts, D; Brener, O; Bursac, N; Tzahor, E

Published Date

  • November 14, 2019

Published In

Volume / Issue

  • 4 / 22

PubMed ID

  • 31723055

Pubmed Central ID

  • PMC6948869

Electronic International Standard Serial Number (EISSN)

  • 2379-3708

International Standard Serial Number (ISSN)

  • 2379-3708

Digital Object Identifier (DOI)

  • 10.1172/jci.insight.128025

Language

  • eng