Coronary artery compliance and adaptive vessel remodelling in patients with stable and unstable coronary artery disease

OBJECTIVE—To test the hypothesis that patients with unstable coronary syndromes show accentuated compensatory vessel enlargement compared with patients with stable angina, and that this may in part be related to increased coronary artery distensibility.
DESIGN AND PATIENTS—In 23 patients with unstable coronary syndromes (10 with non-Q wave myocardial infarction and 13 with unstable angina), the culprit lesion was investigated by intravascular ultrasound before intervention. The vessel cross sectional area (VA), lumen area (LA), and plaque area (VA minus LA) were measured at end diastole and end systole at the lesion site and at the proximal and distal reference segments. Similar measurements were made in 23 patients with stable angina admitted during the same period and matched for age, sex, and target vessel. Calculations were made of remodelling index (VA at lesion site ÷ VA at reference site), distensibility index ([(ΔA/A)/ΔP] × 10³, where ΔA is the luminal area change in systole and diastole and ΔP the difference in systolic and diastolic blood pressure measured at the tip of the guiding catheter during a cardiac cycle), and stiffness index β ([ln(P_sys/P_dias)]/(ΔD/D), where P_sys is systolic pressure, P_dias is diastolic pressure, and ΔD is the difference between systolic and diastolic lumen diameters). Positive remodelling was defined as when the VA at the lesion was > 1.05 times larger than at the proximal reference site, and negative remodelling when the VA at the lesion was < 0.95 of the reference site.
RESULTS—Mean (SD) LA at the lesion site was similar in both groups (4.03 (1.8) v 4.01 (1.93) mm²), while plaque area was larger in the unstable group (13.29 (4.04) v 8.34 (3.6) mm², p < 0.001). Remodelling index was greater in the unstable group (1.14 (0.18) v 0.83 (0.15), p < 0.001). Positive remodelling was observed in 15 patients in the unstable group (65%) but in only two (9%) in the stable group (p < 0.001). Negative remodelling occurred only in two patients with unstable symptoms (9%) but in 17 (74%) with stable symptoms. At the proximal reference segment, the difference in LA between systole and diastole was 0.99 (0.66) mm² in the unstable group and 0.39 (0.3) mm² in the stable group (p < 0.001), and the calculated coronary artery distensibility was 3.09 (2.69) and 0.94 (0.83) per mm Hg in unstable and stable patients, respectively (p < 0.001). The stiffness index β was lower in patients with unstable angina (1.95 (0.94) v 3.1 (0.96), p < 0.001).
CONCLUSIONS—Compensatory vessel enlargement occurs to a greater degree in patients with unstable than with stable coronary syndromes, and is associated with increased coronary artery distensibility.


Keywords: coronary artery disease; remodelling; compliance; angina pectoris     

基质金属蛋白酶9与慢性肺部炎症性疾病

在慢性阻塞性肺疾病、哮喘和肺囊性纤维化等气道慢性炎症性疾病中,常伴有广泛的气道结构破坏,重构和黏液高分泌等病理改变。中性蛋白酶超家族属的基质金属蛋白酶（matrix metalloproteinase,MMP）,因其能裂解结构性蛋白如胶原和弹性蛋白而在这些病理改变中起着重要作用,其中又以MMP-9（又名白明胶酶B）的作用最为突出而成为研究的热点。MMP-9是一种相对分子质量为92000的Ⅳ型胶原酶,能降解基底膜、细胞外基质和弹力纤维,并参与多种肺部炎症反应,近来还发现其可能参与杯状细胞化生和黏液分泌。本文就其在肺部炎性疾病的作用作一综述。     

基质金属蛋白酶9与慢性阻塞性肺疾病

基质金属蛋白酶(matrix metalloproteinase,MMP)是一类高度保守的钙锌离子依赖性内切酶超家族,几乎能够降解细胞外基质(extracellular matrix,ECM)的所有蛋白成分.MMP-9参与肺组织细胞外基质破坏、重塑以及细胞趋化,在慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)的形成、发展、炎症持续方面起了重要作用.寻找毒副作用小、特异性强的MMP-9抑制剂.改善气道重塑,对COPD预防及治疗有重要意义.本文就MMP-9的来源、结构特点、表达与调控以及在COPD发病机制中的作用作一综述.     

动脉损伤后基质金属蛋白酶-3的变化

目的　观察基质金属蛋白酶 3(MMP 3)在动脉球囊损伤后的动态变化 ,探讨MMP 3在再狭窄形成中的作用。方法　建立大鼠腹主动脉球囊损伤模型 ,设立对照组 ,术后第 3d、7d、14d、2 1d、2 8d取材检验 ,应用免疫组织化学法观察MMP 3在血管壁的表达情况。结果　球囊损伤组MMP 3于术后第 3d表达增加 (1 73± 0 2 3) % ,14d达高峰(19 30± 0 32 ) % ,以后逐渐减弱 ;与对照组比较 ,球囊损伤组各时间点均有统计学差异。结论　MMP 3于动脉球囊损伤术后合成、分泌增多 ,在早期再狭窄形成过程中发挥作用     

Soluble adhesion molecules and unstable coronary artery disease

Leukocyte adhesion and transendothelial migration, prerequisites in the development of atherosclerosis, are largely mediated by adhesion molecules. In addition, unstable coronary syndromes usually involve platelet activation and thrombus formation at the site of atherosclerotic plaque. Therefore, we compared plasma levels of soluble P-selectin, a measurement of platelet activation, as well as E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in patients with atherosclerosis undergoing coronary angiography (n=76). Soluble P-selectin levels, as measured by ELISA, were significantly elevated in patients with unstable (n=44) vs stable (n=32) atherosclerotic disease (73.0 +/- 2.5 ng/ml vs 52.3 +/- 3.0 ng/ml, respectively, P<0.01). By logistic regression analysis, plasma level of soluble P-selectin was an independent predictor of an unstable coronary syndrome (OR 4.2, CI 1.4-12.9, P<0.01). Soluble E-selectin level, a marker of endothelial activation, was associated with extent of atherosclerosis but did not correlate with disease stability. Interestingly, soluble P-selectin was inversely correlated with plasma levels of the antioxidant alpha-tocopherol (R=-0.443, P<0.001), a known inhibitor of platelet function. In summary, amongst the soluble adhesion molecules, only P-selectin is significantly increased in patients with unstable coronary syndromes. This study suggests that platelet activation persists in patients with unstable coronary syndromes despite concurrent aspirin therapy. In addition, the beneficial effects of alpha-tocopherol in patients with cardiovascular disease may be related to inhibition of platelet function.     

Testosterone and coronary vascular tone: implications in coronary artery disease

The greater incidence of coronary artery disease in men compared to women has often suggested possible harmful effects of male sex steroids that could promote coronary atherogenesis and vasoconstriction. However, antiatherogenic and coronary vasodilator effects of testosterone have also been suggested. The interaction of testosterone (T) with its specific receptors may trigger not only long-term genomic effects, but also acute non-genomic vasodilator responses. Testosterone may activate the endothelium and stimulate the nitric oxide-cGMP and/or the hyperpolarization-mediated vascular relaxation pathway. T may also inhibit the signaling mechanisms of smooth muscle contraction such as [Ca2+]i and protein kinases. The T-induced stimulation of endothelium-dependent mechanisms of vascular relaxation and inhibition of the mechanisms of coronary smooth muscle contraction represent potential beneficial effects of T against coronary artery disease.     

Leukocyte count and coronary heart disease: implications for risk assessment

Inflammation is a key feature of atherosclerosis and its clinical manifestations. The leukocyte count is a marker of inflammation that is widely available in clinical practice. This paper reviews the available epidemiologic evidence for a relationship between the leukocyte count and coronary heart disease (CHD). Numerous epidemiologic and clinical studies have shown leukocytosis to be an independent predictor of future cardiovascular events, both in healthy individuals free of CHD at baseline and in patients with stable angina, unstable angina, or a history of myocardial infarction. This relationship has been observed in prospective and retrospective cohort studies, as well as in case-control studies. It is strong, consistent, temporal, dose-dependent, and biologically plausible. The relationship persists after adjustment for multiple CHD risk factors, including smoking. Elevated differential cell counts, including eosinophil, neutrophil, and monocyte counts, also predict the future incidence of CHD. Leukocytosis affects CHD through multiple pathologic mechanisms that mediate inflammation, cause proteolytic and oxidative damage to the endothelial cells, plug the microvasculature, induce hypercoagulability, and promote infarct expansion. In summary, leukocytosis has been consistently shown to be an independent risk factor and prognostic indicator of future cardiovascular outcomes, regardless of disease status. The leukocyte count is inexpensive, reliable, easy to interpret, and ordered routinely in inpatient and outpatient settings. However, its diagnostic and prognostic utility in CHD is widely unappreciated. Further studies are needed to assess the true impact of leukocytosis on CHD, compare it with other inflammatory markers such as C-reactive protein and lipoprotein phospholipase A(2) levels, and promote its use in CHD prediction.     

Risk factors for coronary heart disease: implications of gender

It has been recognized over the past years that women form a distinct subpopulation within patients with coronary heart disease. This phenomenon should be acknowledged in the management and in the assessment of coronary heart disease. Over the past years remarkable progress has been made concerning our knowledge of cardiovascular risk factors related to gender. For instance, diabetes, high density lipoproteins and triglycerides levels have been found to have a greater impact on coronary heart disease risk in women compared to men. On the other hand, evidence showing that lipoprotein (a) is a cardiovascular risk factor seems to be stronger in men than in women. For optimal treatment and prevention of coronary heart disease it is necessary to acknowledge that it is not self-evident that women and men show similar responses to risk factors or to treatment. This review article addresses the role of cardiovascular risk factors focusing on the differential impact they might have on men and women.     

Terrorism and the heart: implications for arrhythmogenesis and coronary artery disease

The destruction of the World Trade Center and associated terrorist activities of September 11, 2001 have spurred interest in understanding the medical consequences of terrorist activity. Currently, there is a paucity of data regarding this subject. Potential effects, however, can be garnered by studying the medical effects of other acute stressors, such as earthquakes, missile attacks, and the like. None of these stressors have been studied extensively, but there is enough data available concerning earthquakes to indicate that in some instances, the effects of the earthquake may last at least a period of weeks, if not months, following the earthquake. Since the World Trade Center attack was associated with a rise in post-traumatic stress syndrome and affective disorders afterwards, there is accordingly interest in both the acute and more prolonged health effects that could be engendered following terrorist attacks.Known pathophysiological effects of acute stress, whether produced in a laboratory environment or by studying naturally occurring acute stressors, include: the induction or potentiation of cardiac arrhythmias; the induction of myocardial ischemia in susceptible patients with underlying coronary artery disease; acute increases in arterial blood pressure with its ability to cause shear stress; the precipitation of worsening endothelial function and/or endothelial injury; coagulation abnormalities; and hemoconcentration. These all represent important areas for study following the occurrence of future terrorist activity.Based on existing epidemiological and pathophysiological data concerning the cardiac effects of acute life stressors, it would behoove physicians to closely monitor high-risk cardiac patients following future terrorist events. In addition, physician-scientists should be well prepared to use new epidemiological markers which could provide rapid information following future events, such as the evaluation of patients using pre-versus post-event serum markers or tracing records available among patients fitted with implantable cardiovertor-defibrillators.     

基质金属蛋白酶26与癌

基质金属蛋白酶(matrix metalloproteinase,MMP)是一类高度保守的依赖于锌离子和钙离子的内切蛋白水解酶,几乎能降解构成细胞外基质的所有成分.MMP-26是MMP家族新成员,最早从人子宫内膜癌细胞系cDNA文库克隆成功,其结构和功能与其他成员有许多差异,在癌的发生发展中起着重要的作用.     

Medical therapy versus percutaneous coronary interventions for patients with stable and unstable coronary artery disease

The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial has evoked renewed and intense discussion as to whether to recommend medical therapy or coronary revascularization for patients with coronary artery disease (CAD), especially in those patients with stable CAD who are at low to intermediate risk for future cardiovascular events. The decision in regard to the timing and role of revascularization in patients with unstable CAD, although still evolving, is somewhat less controversial. The major focus of this discussion is, therefore, on the patient with stable CAD.     

Tyrosine phosphorylation of platelet derived growth factor β receptors in coronary artery lesions: implications for vascular remodelling after directional coronary atherectomy and unstable angina pectoris

Background—Growth factors such as platelet derived growth factor (PDGF) have been postulated to be important mediators of neointimal proliferation observed in atherosclerotic plaques and restenotic lesions following coronary interventions. Binding of PDGF to its receptor results in intrinsic receptor tyrosine kinase activation and subsequent cellular migration, proliferation, and vascular contraction.
Aims—To investigate whether the concentration of PDGF β receptor tyrosine phosphorylation obtained from directional coronary atherectomy (DCA) samples correlate with atherosclerotic plaque burden, the ability of diseased vessels to remodel, coronary risk factors, and clinical events.
Methods—DCA samples from 59 patients and 15 non-atherosclerotic left internal thoracic arteries (LITA) were analysed for PDGF β receptor tyrosine phosphorylation content by receptor immunoprecipitation and antiphosphotyrosine western blot. The amount of PDGF β receptor phosphorylation was analysed in relation to angiographic follow up data and clinical variables.
Results—PDGF β receptor tyrosine phosphorylation in the 59 DCA samples was greater than in the 15 non-atherosclerotic LITA (mean (SD) 0.84 (0.67) v 0.17 (0.08) over a control standard, p < 0.0001). As evaluated by stepwise regression analysis, incorporation of both PDGF β receptor tyrosine phosphorylation and immediate gain correlated strongly (adjusted r² = 0.579) with late loss, although PDGF β receptor tyramine phosphorylation alone correlated poorly with late loss. Multivariate regression analysis of coronary risk factors and clinical events revealed unstable angina as the most significant correlate of PDGF β receptor tyrosine phosphorylation (F value 20.009, p < 0.0001).
Conclusions—PDGF β receptor tyrosine phosphorylation in atherosclerotic lesions is increased compared with non-atherosclerotic arterial tissues. The association of PDGF β receptor tyrosine phosphorylation with immediate gain strongly correlates with vascular remodelling. PDGF β receptor tyrosine phosphorylation correlates with unstable angina pectoris.

Keywords: PDGF receptors;  atherosclerosis;  directional coronary atherectomy;  restenosis