A single intravenous bolus of n-apo AI (80 mg/kg) reduced circulating leukocytes by 30±7% in mice post-myocardial infarction and by 12±5% in patients with type 2 diabetes (P<0.05).
Does n-apo AI reduce systemic and cardiac inflammatory response in a mouse model of myocardial infarction and patients with type 2 diabetes?
A single intravenous bolus of n-apo AI delivered immediately post-myocardial infarction reduces systemic and cardiac inflammation, providing preclinical support for its use in acute coronary syndromes.
Effect estimate: 30±7% reduction in mice; 12±5% reduction in humans
p-value: p=<5.0×10^-2
Rationale: Decades of research have examined immune-modulatory strategies to protect the heart after an acute myocardial infarction and prevent progression to heart failure but have failed to translate to clinical benefit. Objective: To determine anti-inflammatory actions of n-apo AI (Apo AI nanoparticles) that contribute to cardiac tissue recovery after myocardial infarction. Methods and Results: Using a preclinical mouse model of myocardial infarction, we demonstrate that a single intravenous bolus of n-apo AI (CSL111, 80 mg/kg) delivered immediately after reperfusion reduced the systemic and cardiac inflammatory response. N-apo AI treatment lowered the number of circulating leukocytes by 30±7% and their recruitment into the ischemic heart by 25±10% (all P <5.0×10 −2 ). This was associated with a reduction in plasma levels of the clinical biomarker of cardiac injury, cardiac troponin-I, by 52±17% ( P =1.01×10 −2 ). N-apo AI reduced the cardiac expression of chemokines that attract neutrophils and monocytes by 60% to 80% and lowered surface expression of integrin CD11b on monocytes by 20±5% (all P <5.0×10 −2 ). Fluorescently labeled n-apo AI entered the infarct and peri-infarct regions and colocalized with cardiomyocytes undergoing apoptosis and with leukocytes. We further demonstrate that n-apo AI binds to neutrophils and monocytes, with preferential binding to the proinflammatory monocyte subtype and partially via SR-BI (scavenger receptor BI). In patients with type 2 diabetes, we also observed that intravenous infusion of the same n-apo AI (CSL111, 80 mg/kg) similarly reduced the level of circulating leukocytes by 12±5% (all P <5.0×10 −2 ). Conclusions: A single intravenous bolus of n-apo AI delivered immediately post–myocardial infarction reduced the systemic and cardiac inflammatory response through direct actions on both the ischemic myocardium and leukocytes. These data highlight the anti-inflammatory effects of n-apo AI and provide preclinical support for investigation of its use for management of acute coronary syndromes in the setting of primary percutaneous coronary interventions.
Richart et al. (Mon,) conducted a other in Myocardial infarction and Type 2 diabetes. n-apo AI (CSL111) was evaluated on Systemic and cardiac inflammatory response (circulating leukocytes) (30±7% reduction in mice; 12±5% reduction in humans, p=<5.0×10^-2). A single intravenous bolus of n-apo AI (80 mg/kg) reduced circulating leukocytes by 30±7% in mice post-myocardial infarction and by 12±5% in patients with type 2 diabetes (P<0.05).