Immune and Inflammation in Acute Coronary Syndrome: Molecular Mechanisms and Therapeutic Implications

Abstract

Acute coronary syndrome (ACS) is a major cause of acute death worldwide. Both innate and adaptive immunity regulate atherosclerosis progression, plaque stability, and thrombus formation. Immune and inflammation dysfunction have been indicated in the pathogenesis of ACS. The imbalance in the proatherogenic and antiatherogenic immune networks promotes the transition of plaques from a stable to unstable state and results in the occurrence of acute coronary events. The residual inflammatory risk (RIR) has received increasing attention in recent years, and lowering RIR has been expected to improve the outcomes of ACS patients. The CANTOS, COLCOT, and LoDoCo trials verified the benefits of reducing cardiovascular events using anti-inflammation therapies; however, most of the other studies focusing on lowering RIR produced negative or contradicting results. Therefore, restoring the balance in autoimmune regulation is essential because proatherogenic and antiatherogenic immunomodulatory effects are equally important in the complex human immune network. In this review, we summarized the recent evidence of the roles of proatherogenic and antiatherogenic immune networks in the pathogenesis of ACS and discussed how immune and inflammation contribute to atherosclerosis progression, plaque instability, and adverse cardiovascular events. We also provide a “from bench to bedside” perspective of a novel and promising personalized strategy in RIR intervention and therapeutic approaches for the treatment of ACS.

Anti-inflammatory Therapies for Coronary Heart Disease: A Systematic Review and Meta-Analysis

“…The attainment of cardiovascular benefits is compromised by the limitations of available treatment for CHD ( 1 , 2 , 8 , 28 ). Although low-density lipoprotein-cholesterol lowering and antiplatelet therapies have been widely recommended by guidelines and administered in clinical practice, more than half of CHD patients have a high level of hsCRP, a direct metric of systemic inflammation, to drive the natural history of this disease ( 2 , 29 , 30 ). Persistent residual inflammatory risk destabilizes atherosclerotic plaques and exacerbates the risk of MACEs ( 2 ).…”

“…Although low-density lipoprotein-cholesterol lowering and antiplatelet therapies have been widely recommended by guidelines and administered in clinical practice, more than half of CHD patients have a high level of hsCRP, a direct metric of systemic inflammation, to drive the natural history of this disease ( 2 , 29 , 30 ). Persistent residual inflammatory risk destabilizes atherosclerotic plaques and exacerbates the risk of MACEs ( 2 ). In the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) trial, patients with CHD were more prone to develop adverse cardiovascular events when proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors were used to reduce low-density lipoprotein cholesterol (LDL-C) to a lower level but hsCRP levels exceeded the upper limit of normal ( 28 , 31 ).…”

“…This finding was consistent with a recently published meta-analysis focusing on stable CHD patients ( 5 ). These data could be interpreted by the pathogenesis of coronary atherosclerotic plaques that consists of a large lipid core and thin fibrous cap involving activated immune cells and inflammatory cytokines ( 2 , 33 – 35 ). In the phase of plaque progression, anti-inflammatory therapy targeting inflammatory factors renders patients more susceptible to stabilization ( 2 , 35 , 36 ).…”

“…Coronary heart disease (CHD) is a progressive clinical syndrome that is associated with an enhanced risk of fatal myocardial infarction, stroke, revascularization or cardiogenic death ( 1 , 2 ). The available treatments recommended by the guidelines have not been reliably shown to further alter this clinical course ( 1 , 3 ).…”

“…The available treatments recommended by the guidelines have not been reliably shown to further alter this clinical course ( 1 , 3 ). Recent evidence has indicated that residual inflammatory risk (RIR) accelerates the progression of CHD by modulating immune cells and inflammatory cytokines ( 2 , 4 ). A series of clinical studies have attempted to evaluate the efficacy of various anti-inflammatory agents in CHD patients ( 5 , 6 ).…”