Triggering Of Acute Coronary Syndromes Research Articles

Genetically determined resistance to collagenase action augments interstitial collagen accumulation in atherosclerotic plaques.

We hypothesized that collagenolytic activity produced by activated macrophages contributes to collagen loss and the subsequent instability of atheromatous lesions, a common trigger of acute coronary syndromes. However, no direct in vivo evidence links collagenases with the regulation of collagen content in atherosclerotic plaques. To test the hypothesis that collagenases influence the structure of atheromata, we examined collagen accumulation in atherosclerotic lesions of apolipoprotein E-deficient mice (apoE-/-) that express collagenase-resistant collagen-I (ColR/R/apoE-/-, n=12) or wild-type collagen-expressing mice (Col+/+/apoE-/-, n=12). Aortic atheromata of both groups had similar sizes and numbers of macrophages, a major source of collagenases. However, aortic intimas from ColR/R/apoE-/- mice contained fewer smooth muscle cells, a source of collagen, probably because of decreased migration or proliferation or increased cell death. Despite reduced numbers of smooth muscle cells, atheromata of ColR/R/apoE-/- mice contained significantly more intimal collagen than did those of Col+/+/apoE-/- mice. These results establish that collagenase action regulates plaque collagen turnover and smooth muscle cell accumulation.

Exaggerated platelet and hemodynamic reactivity to mental stress in men with coronary artery disease.

This study compared the effects of acute mental stress on cardiovascular and subjective responses and platelet activation in male patients with established coronary artery disease (CAD) and age-matched controls. We assessed 17 male CAD patients aged 44 to 59 years and 22 healthy male controls. Blood pressure, heart rate, and hemodynamics were assessed before, during, and up to 2 hours after administration of color/word and mirror tracing tasks. Blood was sampled at baseline, after tasks, and at 30 and 75 minutes after stress, and platelet activation was assessed by measuring platelet-leukocyte aggregates (PLAs) using flow cytometry. CAD patients showed significantly greater systolic blood pressure stress responses than controls (mean increases of 43.9 and 28.3 mm Hg, adjusted for income, body mass index, waist/hip ratio, and medication), together with larger increases in heart rate (14.1 and 4.7 bpm) and cardiac index. Total peripheral resistance increased during the poststress recovery period in CAD patients but not in controls. PLAs increased with stress in both groups, but remained elevated at 75 minutes in CAD patients, returning to baseline in controls. Heart rate and cardiac index responses were correlated with increases in subjective stress and with depression ratings, whereas PLA responses were associated with ratings of task difficulty. Acute mental stress stimulated heightened cardiovascular responses in CAD patients, coupled with more prolonged platelet activation. These factors may contribute to plaque rupture and thrombogenesis, and partly mediate stress-induced triggering of acute coronary syndromes.

Natural phenolic compounds as cardiovascular therapeutics: potential role of their antiinflammatory effects.

A number of epidemiological studies have shown that diets rich in plant-derived phenolic compounds reduce the risk of coronary heart disease. The chronic antioxidant and hypolipidemic activities of these compounds have important roles in prevention of lipoprotein oxidation and atherosclerotic lesion development. In recent years, it has been recognized that inflammation is directly involved in development of cardiovascular disease and clinical events such as atherosclerotic plaque rupture (which is the trigger of acute coronary syndrome), arterial restenosis, and myocardial ischemia-reperfusion injury. Phenolic compounds have significant antiinflammatory effects, including inhibition of adhesion molecule, cytokine and chemokine gene expression; inhibition of platelet function; augmentation of endothelial nitric oxide release; suppression of smooth muscle activation; and other effects on proinflammatory factors such as endothelin and matrix metalloproteinases. However, direct evidence of acute therapeutic benefits of phenolic compounds in cardiovascular disorders remains sparse. This review attempts to integrate the inflammatory mechanisms involved in these cardiovascular diseases with recent findings on the antiinflammatory effects of phenolic compounds. Findings from the limited in vivo studies in this regard are discussed. It is suggested that searching for novel phenolic compounds with higher specificity and efficacy may represent a fruitful approach in development of new cardiovascular therapeutics.

Is there a vulnerable plaque?

The identification of potential triggers of acute coronary syndromes (ACS) represented by unstable angina (UA), myocardial infarction (MI) (preceded or not by UA), and sudden coronary death (SCD) is a rapidly growing area of research. Coronary plaque disruption and subsequent thrombosis is the major recognized pathogenetic component of “unstable plaques,” which characterize the transition from stable coronary artery disease (CAD) to ACS. However, in the presence of unstable or even stable plaques, a thrombogenic state or “high-risk blood” may contribute, at least in some cases, to the development of ACS.1 Furthermore, thrombosis is also an integral component of the chronic atherothrombotic progression of atherosclerosis. Although the observation that plaque disruption leads to ACS goes back a number of decades, the notion of “vulnerable plaques” was first developed a little over a decade ago on the basis of post-mortem observations in patients with ACS.2 At the site of culprit coronary lesions, a rupture was often found at the shoulder of atheromatous plaques with a large pultaceous lipid core and a thin fibrous cap. Such rupture was originally thought to be the result of localized mechanical shear stress forces.3 However, on the basis of emerging evidence of a prevalent inflammatory component in ACS, inflammatory mechanisms of plaque instability began to receive considerable attention.4 The acquisition of knowledge does not necessarily makes things more comprehensible, but rather often adds novel complexities. Yet, when confronted with a pressing issue, such as predicting major future adverse events, there is a natural inclination to accept generalizations not yet justified by available data. The intriguing concept of a vulnerable plaque, as a potential short-term precursor of unstable plaques, derives from the theoretical possibility of identifying those coronary atherosclerotic plaques that might become unstable and thus trigger ACS. The notion of vulnerable plaques is …

Triggers of acute coronary syndromes

Despite recent progress in prevention of coronary heart disease, approximately 50% of the deaths from coronary artery disease continue to occur out of hospital, and many major cardiac events occur in individuals not previously known to be at risk. These facts create the need to identify the acute causes of myocardial infarction (MI) and sudden death, which has led to a rapid growth in interest over the last 15 years in the field of triggering research. Since initial observations that the incidence of MI onset was time and activity dependent with circadian, circaseptan, and circannual variation, triggering of MI by heavy exertion, sexual activity, anger, mental stress, cocaine and marijuana use, and exposure to air pollution has been demonstrated. Study of the pathophysiological changes produced by these triggers may provide novel therapeutic and preventive targets by a more thorough understanding of vulnerable plaque disruption and coronary thrombosis. Copyright 2002, Elsevier Science (USA). All rights reserved.

Activation of haemostasis by exercise, mental stress and adrenaline: effects on platelet sensitivity to thrombin and thrombin generation

Stress-induced activation of haemostasis may be involved in the triggering of acute coronary syndromes. We compared the effects of mental stress, dynamic exercise and adrenaline infusion on platelet sensitivity to thrombin using flow-cytometric analysis of platelet fibrinogen binding in whole blood, and platelet aggregability using filtragometry ex vivo, in healthy volunteers. Furthermore, we assessed thrombin generation [prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complexes in plasma] and thrombin activity (fibrinopeptide A in plasma). Exercise (bicycle ergometry) enhanced thrombin-induced platelet fibrinogen binding (P<0.05) and platelet aggregability (P<0.01), and elevated F1+2, thrombin-antithrombin complexes and fibrinopeptide A (P<0.05 for all three). Adrenaline infusion enhanced thrombin-induced platelet fibrinogen binding and platelet aggregability (P<0.05), and elevated thrombin-antithrombin complexes (P<0.05), whereas F1+2 and fibrinopeptide A levels were not significantly affected. Mental stress increased platelet sensitivity to high concentrations of thrombin only, and produced small increases in levels of thrombin-antithrombin complexes. Time control experiments showed no important changes with repeated measurements during rest. Platelet responses to exercise and adrenaline were reversible, with recovery 60 min later. Thus, heavy exercise and high levels of adrenaline reversibly increased platelet aggregability and platelet sensitivity to thrombin, and enhanced thrombin formation; the effects were most pronounced during exercise. Mental stress only weakly affected these parameters.