Inflammation in Coronary Atherosclerosis and Its Therapeutic Implications

Montarello, Natalie; Nguyen, Mau T.; Wong, D.; Nicholls, Stephen J.; Psaltis, Peter J.

doi:10.1007/s10557-020-07106-6

Cited by 33 publications

(30 citation statements)

References 176 publications

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“…Considered a chronic inflammatory disease of blood vessels, atherosclerosis is characterized by a maladaptive immune response, triggered by subintimal lipoprotein accumulation, and resulting in the formation of lipid-rich, inflamed plaques [9]. Ultimately, systemic and local activation of both the adaptive and innate immune systems can result in either rupture or erosion of an atherosclerotic plaque, leading to thrombosis, which may manifest as unstable angina, acute MI or sudden cardiac death [15,16].…”

Section: Coronary Atherosclerosis: An Inflammatory Process Requiring Treatment Beyond Statinsmentioning

confidence: 99%

“…Inflammation is independently and strongly associated with future MACE in both primary and secondary prevention settings [5][6][7][8]. Current therapies for CAD, such as lipid-lowering statins, do not adequately control plaque inflammation, meaning that new anti-atherosclerotic agents targeting inflammation are needed [9]. The positive results for the anti-interleukin-1-beta (IL-1β) monoclonal antibody, canakinumab, in the CANTOS clinical trial [10], highlighted that not only is inflammation important from a pathogenic and risk prediction perspective in CAD, but that reducing inflammation can be beneficial.…”

Section: Introductionmentioning

confidence: 99%

“…More recently, low-dose colchicine, a broad acting anti-inflammatory agent, has been repurposed for the treatment of CAD. Results from the LoDoCo [11], LoDoCo 2 [12], COPS [13] and COLCOT [14] studies have demonstrated potential clinical benefit of colchicine use in patients with both stable and unstable CAD, with other Phase 3 clinical studies still ongoing [9]. Colchicine's potential mechanism of effect in atherosclerosis is protean, and although it may primarily act via its known action on innate immune pathways, we hypothesize that it may also promote favourable plaque healing following MI, leading to the formation of a thicker plaque cap which is more resilient to rupture and thrombosis.…”

Section: Introductionmentioning

confidence: 99%

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Assessing the Impact of Colchicine on Coronary Plaque Phenotype After Myocardial Infarction with Optical Coherence Tomography: Rationale and Design of the COCOMO-ACS Study

Montarello

Singh

Sinhal

et al. 2021

Cardiovasc Drugs Ther

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Introduction Recurrent event rates after myocardial infarction (MI) remain unacceptably high, in part because of the continued growth and destabilization of residual coronary atherosclerotic plaques, which may occur despite lipid-lowering therapy. Inflammation is an important contributor to this ongoing risk. Recent studies have shown that the broad-acting anti-inflammatory agent, colchicine, may reduce adverse cardiovascular events in patients post-MI, although the mechanistic basis for this remains unclear. Advances in endovascular arterial wall imaging have allowed detailed characterization of the burden and compositional phenotype of coronary plaque, along with its natural history and responsiveness to treatment. One such example has been the use of optical coherence tomography (OCT) to demonstrate the plaque-stabilizing effects of statins on both fibrous cap thickness and the size of lipid pools within plaque. Methods The Phase 2, multi-centre, double-blind colchicine for coronary plaque modification in acute coronary syndrome (COCOMO-ACS) study will evaluate the effect of colchicine 0.5 mg daily on coronary plaque features using serial OCT imaging in patients following MI. Recruitment for the trial has been completed with 64 participants with non-ST elevation MI randomized 1:1 to colchicine or placebo in addition to guideline recommended therapies, including high-intensity statins. The primary endpoint is the effect of colchicine on the minimal fibrous cap thickness of non-culprit plaque over an 18-month period. Summary The COCOMO-ACS study will determine whether addition of colchicine 0.5 mg daily to standard post-MI treatment has incremental benefits on high-risk features of coronary artery plaques. If confirmed, this will provide new mechanistic insights into how colchicine may confer clinical benefits in patients with atherosclerotic cardiovascular disease. Trial Registration ANZCTR trial registration number: ACTRN12618000809235. Date of trial registration: 11th of May 2018.

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Section: Coronary Atherosclerosis: An Inflammatory Process Requiring Treatment Beyond Statinsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Assessing the Impact of Colchicine on Coronary Plaque Phenotype After Myocardial Infarction with Optical Coherence Tomography: Rationale and Design of the COCOMO-ACS Study

Montarello

Singh

Sinhal

et al. 2021

Cardiovasc Drugs Ther

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“…The progressive slow-growth plaques lead to narrowing and hardening of arteries and rupture or erosion of existing plaques may result in acute arterial occlusion by subsequent thrombus formation ( Nettersheim et al, 2020 ). These pathological events are one of the most critical risk factors in various cardiovascular diseases like ischemic heart disease, cerebrovascular disease, and peripheral artery disease ( Montarello et al, 2020 ). Multiple studies have indicated that abnormal inflammation and lipid metabolism promote plaque formation in blood vessel wall of arteries.…”

Section: Introductionmentioning

confidence: 99%

NLRP3-Mediated Inflammation in Atherosclerosis and Associated Therapeutics

Cheng

Liu

et al. 2022

Front. Cell Dev. Biol.

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The NLRP3 inflammasome is a crucial constituent of the body’s innate immune system, and a multiprotein platform which is initiated by pattern recognition receptors (PRRs). Its activation leads to caspase-1 maturation and release of inflammatory cytokines, interleukin-1β (IL-1β) and IL-18, and subsequently causes pyroptosis. Recently, the excess activation of NLRP3 inflammasome has been confirmed to mediate inflammatory responses and to participate in genesis and development of atherosclerosis. Therefore, the progress on the discovery of specific inhibitors against the NLRP3 inflammasome and the upstream and downstream inflammatory factors has become potential targets for clinical treatment. Here we review the recently described mechanisms about the NLRP3 inflammasome activation, and discuss emphatically the pharmacological interventions using statins and natural medication for atherosclerosis associated with NLRP3 inflammasome.

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“…It is a progressive and chronic disease modulated by environmental and genetic factors [2]. Several studies have proposed liver enzymes as cardiovascular disease (CVD) markers [3][4][5]. Transaminases are not traditional cardiovascular risk factors; however, it has been observed that elevated concentrations of liver enzymes have been associated with mortality from cardiovascular disease.…”

Section: Introductionmentioning

confidence: 99%

Association of the IL-37 Polymorphisms with Transaminases and Alkaline Phosphatase Levels in Premature Coronary Artery Disease Patients and Healthy Controls. Results of the Genetics of Atherosclerotic (GEA) Mexican Study

2021

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Interleukin 37 (IL-37) is an anti-inflammatory cytokine expressed in foam cells located in the atherosclerosis plaques. The present study aimed to evaluate the association of the IL-37 polymorphisms with premature coronary artery disease (pCAD), cardiovascular risk factors, metabolic parameters, and levels of liver enzymes. Three IL-37 polymorphisms (rs6717710, rs2708961, and rs2708947) were determined in 1161 patients with pCAD and 951 healthy controls. IL-37 polymorphisms were not associated with the presence of pCAD. The association of the polymorphisms with cardiovascular risk factors, metabolic parameters, and levels of liver enzymes was evaluated independently in pCAD and healthy controls. In pCAD patients, under different models, the rs6717710 was associated with low risk of having elevated alkaline phosphatase (ALP) (padditive = 0.020; pdominant = 0.02; pheterozygous = 0.04; pcodominant1 = 0.040). On the other hand, in healthy controls, the rs6717710 was associated with low risk of having elevated levels of alanine aminotransferase (ALT) (padditive = 0.04, precessive = 0.01, pcodominant2 = 0.01) and aspartate aminotransferase (AST) (padditive = 0.02, pdominant = 0.02). The IL-37 polymorphisms were not associated with the risk of pCAD. In pCAD patients, the rs6717710 was associated with low risk of having elevated ALP levels, whereas in controls was associated with low risk of having elevated ALT and AST levels.

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Inflammation in Coronary Atherosclerosis and Its Therapeutic Implications

Cited by 33 publications

References 176 publications

Assessing the Impact of Colchicine on Coronary Plaque Phenotype After Myocardial Infarction with Optical Coherence Tomography: Rationale and Design of the COCOMO-ACS Study

Assessing the Impact of Colchicine on Coronary Plaque Phenotype After Myocardial Infarction with Optical Coherence Tomography: Rationale and Design of the COCOMO-ACS Study

NLRP3-Mediated Inflammation in Atherosclerosis and Associated Therapeutics

Association of the IL-37 Polymorphisms with Transaminases and Alkaline Phosphatase Levels in Premature Coronary Artery Disease Patients and Healthy Controls. Results of the Genetics of Atherosclerotic (GEA) Mexican Study

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