Objective Factors and mechanisms that activate macrophages in atherosclerotic plaques are incompletely understood. We examined the capacity of heparanase to activate macrophages. Results/Methods Highly purified heparanase was added to mouse peritoneal macrophages (MPM) and macrophage-like J774 cells and the levels of TNFα, MMP-9, IL-1, and MCP-1 were evaluated by ELISA. Gene expression was determined by RT-PCR. Cells collected from Toll like receptor (TLR)-2 and -4 knockout mice (KO) were evaluated similarly. Heparanase levels in the plasma of patients with acute myocardial infarction (MI), stable angina (SA), and healthy subjects were determined by ELISA. Immunohistochemistry was applied to detect the expression of heparanase in control specimens and specimens of patients with SA or acute MI. Addition or over expression of heparanase variants resulted in marked increase in TNFα, MMP-9, IL-1 and MCP-1 levels. MPM harvested from TLR-2 or TLR-4 knockout mice were not activated by heparanase. Plasma heparanase level was higher in patients with acute MI, compared to patients with SA and healthy subjects. Pathologic coronary specimens obtained from vulnerable plaques showed increased heparanase staining compared to specimens of stable plaque and controls. Conclusion Heparanase activates macrophages, resulting in marked induction of cytokine expression associated with plaque progression towards vulnerability.

There have been reports of myocarditis following COVID-19 vaccination. We surveyed all hospitalized military personnel in the Isareli Defense Forces during the period of the COVID-19 vaccination operation (12/28/2021-3/7/2021) for diagnosed myocarditis. We identified 7 cases of myocarditis with symptoms starting in the first week after the second dose of COVID-19 Pfizer-BioNTech vaccine. One case of myocarditis diagnosed 10 days after the second dose of the vaccine was not included. These 8 cases comprise of all events of myocarditis diagnosed in military personnel during this time period. All patients were young and generally healthy. All had mild disease with no sequalae. The incidence of myocarditis in the week following a second dose of the vaccine was 5.07/100,000 people vaccinated. Due to the nature of this report no causality could be established. Clinicians should be aware of the possibility of myocarditis following Pfizer-BioNTech vaccination. True incidence rates should be further investigated.

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