Pathogenesis of Acute Coronary Syndromes Crea, Filippo, MD; Liuzzo, Giovanna, MD, PhD
Journal of the American College of Cardiology,
01/2013, Letnik:
61, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Experimental models of atherogenesis have provided a growing body of information about molecular mechanisms of plaque growth; however, transition from coronary stability to instability is less well ...understood due to the lack of animal models reflective of human disease. The abrupt clinical presentation of acute coronary syndromes gives a strong signal of discontinuity in the natural history of atherothrombosis. The causes of such discontinuity are complex, probably multiple, and still largely unknown. A better knowledge of the causes of coronary instability might allow identification of new therapeutic targets aimed at the preservation of plaque stability in those subjects in whom primary prevention fails to prevent plaque growth. The goal of this review was to propose a pathogenetic classification of acute coronary syndromes that might help in the search of new diagnostic algorithms and therapeutic targets.
Superficial erosion currently causes at least one-third of acute coronary syndromes (ACS), and its incidence is increasing. Yet, the underlying mechanisms in humans are still largely unknown.
The ...authors sought to assess the role of hyaluronan (HA) metabolism in ACS.
Peripheral blood mononuclear cells were collected from ACS (n = 66), stable angina (SA) (n = 55), and control (CTRL) patients (n = 45). The authors evaluated: 1) gene expression of hyaluronidase 2 (HYAL2) (enzyme degrading high-molecular-weight HA to its proinflammatory 20-kDa isoform) and of CD44v1, CD44v4, and CD44v6 splicing variants of HA receptor; and 2) HYAL2 and CD44 protein expression. Moreover, they compared HYAL2 and CD44 gene expression in ACS patients with plaque erosion (intact fibrous cap and thrombus) and in ACS patients with plaque rupture, identified by optical coherence tomography analysis.
Gene expression of HYAL2, CD44v1, and CD44v6 were significantly higher in ACS as compared with SA (p = 0.003, p < 0.001, and p = 0.033, respectively) and CTRL subjects (p < 0.001, p < 0.001, and p = 0.009, respectively). HYAL2 protein expression was significantly higher in ACS than in SA (p = 0.017) and CTRL (p = 0.032), whereas no differences were found in CD44 protein expression. HYAL2 and CD44v6 gene expression was significantly higher in patients with plaque erosion than in those with plaque rupture (p = 0.015 and p = 0.029, respectively).
HYAL2 and CD44v6 splicing variants seem to play an important role in ACS, in particular when associated with plaque erosion. After further validation, HYAL2 might represent a potentially useful biomarker for the noninvasive identification of this mechanism of coronary instability.
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Type 2 diabetes mellitus (DM) represents, with its macro and microvascular complications, one of the most critical healthcare issues for the next decades. Remarkably, in the context of regulatory ...approval trials, sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) proved a reduced incidence of major adverse cardiovascular events (MACEs), i.e., cardiovascular death and heart failure (HF) hospitalizations. The cardioprotective abilities of these new anti-diabetic drugs seem to run beyond mere glycemic control, and a growing body of evidence disclosed a wide range of pleiotropic effects. The connection between diabetes and meta-inflammation seems to be the key to understanding how to knock down residual cardiovascular risk, especially in this high-risk population. The aim of this review is to explore the link between meta-inflammation and diabetes, the role of newer glucose-lowering medications in this field, and the possible connection with their unexpected cardiovascular benefits.
Background
Coronary vasomotor dysfunction represents an important mechanism responsible for myocardial ischaemia in patients with non-obstructive coronary artery disease (CAD). The use of invasive ...provocative tests allows identifying patients with epicardial or microvascular spasm. Of note, clinical characteristics associated with the occurrence of epicardial or microvascular spasm have still not completely clarified.
Methods and results
We prospectively enrolled consecutive patients undergoing coronary angiography for suspected myocardial ischaemia/necrosis with evidence of non-obstructive CAD and undergoing intracoronary provocative test for suspected vasomotor dysfunction. Patients with a positive provocative test were enrolled. Clinical, echocardiographic and angiographic characteristics of patients were evaluated according to the pattern of vasomotor dysfunction (epicardial vs. microvascular spasm). We included 120 patients 68 patients with stable angina and 52 patients with myocardial infarction and non-obstructive coronary arteries (MINOCA). In particular, 77 (64.2%) patients had a provocative test positive for epicardial spasm and 43 (35.8%) patients for microvascular spasm. Patients with epicardial spasm were more frequently males, smokers, had higher rates of diffuse coronary atherosclerosis at angiography and more frequently presented with MINOCA. On the other hand, patients with microvascular spasm presented more frequently diastolic dysfunction. At multivariate logistic regression analysis male sex, smoking, and diffuse coronary atherosclerosis were independent predictors for the occurrence of epicardial spasm.
Conclusions
Our study showed that specific clinical features are associated with different responses to intracoronary provocative test. Epicardial spasm is more frequent in males and in MINOCA patients, whereas microvascular spasm is more frequent in patients with stable angina and is associated with diastolic dysfunction.
Inflammation is the main pathophysiological process involved in atherosclerotic plaque formation, progression, instability, and healing during the evolution of coronary artery disease (CAD). The use ...of colchicine, a drug used for decades in non-ischemic cardiovascular (CV) diseases and/or systemic inflammatory conditions, stimulated new perspectives on its potential application in patients with CAD. Previous mechanistic and preclinical studies revealed anti-inflammatory and immunomodulatory effects of colchicine exerted through its principal mechanism of microtubule polymerization inhibition, however, other pleiotropic effects beneficial to the CV system were observed such as inhibition of platelet aggregation and suppression of endothelial proliferation. In randomized double-blinded clinical trials informing our clinical practice, low doses of colchicine were associated with the significant reduction of cardiovascular events in patients with stable CAD and chronic coronary syndrome (CCS) while in patients with a recent acute coronary syndrome (ACS), early initiation of colchicine treatment significantly reduced major adverse CV events (MACE). On the other hand, the safety profile of colchicine and its potential causal relationship to the observed increase in non-CV deaths warrants further investigation. For these reasons, postulates of precision medicine and patient-tailored approach with regards to benefits and harms of colchicine treatment should be employed at all times due to potential toxicity of colchicine as well as the currently unresolved signal of harm concerning non-CV mortality. The main goal of this review is to provide a balanced, critical, and comprehensive evaluation of currently available evidence with respect to colchicine use in the setting of CAD.
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