OC 64.2 - Platelet releasate attenuates ischemic damage in acute myocardial infarction in mice

Background: Acute myocardial infarction (AMI) is a leading cause of mortality worldwide. Ischemic damage to the ventricular wall includes inflammation, widespread cell death, proliferation of fibroblasts and accumulation of collagen in fibrosis. Here we investigated potential reparative and protective roles that platelets may play in AMI.

Aims: It is well documented that activated platelets secrete numerous factors from their granules including chemokines, cytokines and growth factors, and additionally shed large numbers of extracellular vesicles. We sought to investigate whether the platelet releasate plays any positive role in cardiac remodelling following AMI in mice.

Methods: Mouse platelet releasate (PR) was generated by activating washed mouse platelets in vitro followed by a rapid spin and supernatant obtained (PR). Mouse AMI was generated by surgical ligation of the left anterior descending branch of the left coronary artery (LAD) and 25 microlitres of PR or control buffer were injected into the ischemic area of the left ventricle (LV) and mouse cardiac functions were monitored by echocardiography for 3 weeks post-surgery. Cardiac tissue damage and fibrosis in the LV were assessed by histological staining and microscopic imaging.

Results: Our results showed that in a mouse AMI model intra-myocardial injection of PR resulted in marked beneficial effects including attenuation of ischemic damage, reduction in fibrosis and retention of cardiac function compared to control buffer. All cardiac functions assessed by echocardiography in the PR group were significantly better compared to controls (Fig 1) and histology also showed that PR injected hearts were of smaller infarct size and lower levels of fibrosis in the LV than the control group (Fig 2).

Conclusion(s): Our results indicate that activated platelets at the site of ischemic myocardium could provide substantial beneficial effects by release of factors, including those from granules, but possibly also including extracellular vesicles.