The small molecule Chicago Sky Blue promotes heart repair following myocardial infarction in mice
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Updated: Jan 3, 2026
An Experimental Model of Myocardial Infarction for Studying Cardiac Repair and Remodeling in Knockout Mice
Published on: July 14, 2023
Oren Yifa1, Karen Weisinger1, Elad Bassat1
1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Insights
A novel small molecule, Chicago Sky Blue 6B (CSB), enhances heart repair after injury in mice. CSB reduces scar size and improves heart function by modulating inflammation and signaling pathways.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Pharmacology
Background:
- Adult mammalian heart regeneration is limited after injury, contributing to high mortality from ischemic heart diseases.
- Cardiac repair involves complex processes like inflammation, fibrosis, and cardiomyocyte function, which are potential therapeutic targets.
Purpose of the Study:
- To identify small molecules that promote cardiomyocyte proliferation in vitro.
- To evaluate the therapeutic potential of identified compounds in a mouse model of myocardial infarction.
Main Methods:
- Developed an automated high-throughput screening system to identify pro-proliferative small molecules for cardiomyocytes.
- Administered the identified small molecule, Chicago Sky Blue 6B (CSB), to adult mice following induced myocardial infarction.
- Assessed cardiac function, scar size, inflammatory cell activation, and signaling pathways (CaMKII).
Main Results:
- Identified Chicago Sky Blue 6B (CSB) as a small molecule that can induce cardiomyocyte proliferation in vitro.
- CSB treatment significantly reduced scar size and improved cardiac function in adult mice post-myocardial infarction.
- CSB inhibited CaMKII signaling, enhancing cardiomyocyte contractility, and suppressed neutrophil and macrophage activation, reducing acute inflammation.
Conclusions:
- Chicago Sky Blue 6B (CSB) is a promising therapeutic agent for enhancing cardiac repair and function after injury.
- CSB promotes heart repair by suppressing detrimental post-injury processes, including inflammation and aberrant signaling, rather than inducing cardiomyocyte renewal.
Abstract:
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.
