李洁
中国医学科学院阜外医院 病房
C-reactive protein (CRP) is well-known inflammatory marker, and recognized as a risk predictor of pulmonary arterial diseases. Although statins have a beneficial effect in animal models and patients with pulmonary arterial hypertension (PAH), the underlying mechanisms of their actions have less been investigated. The aims of this study was to examined the effects of CRP on expressions of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1), and the possible mechanisms of atorvastatin on CRP-induced IL-6 and MCP-1 production in cultured human pulmonary artery smooth muscle cells (PASMCs). In a preliminary study, the human PASMCs were stimulated by a variety of concentrations of CRP (5-200 microg/mL) at different time points (0, 3, 6, 9, 12, 18 and 24 h) for the purpose of determining the dose- and time-dependent effects of CRP on inflammatory response of the cells. Then, the cells were pre-incubated for 2 h with atorvastatin (0.1-10 micromol/L) in the presence of CRP. The supernatant levels of both IL-6 and MCP-1 secretion were examined by ELISA. The cellular mRNA expressions of IL-6 and MCP-1 and nuclear factor-kappaB (NF-kappaB) activity were determined by real-time reverse transcription and polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay (EMSA), respectively. CRP resulted in elevated IL-6 and MCP-1 secretion and mRNA expression in a dose- and time-dependent manner. In addition, CRP also significantly activated the NF-kappaB pathway. Preincubation with 0.1-10 micromol/L of atorvastatin significantly decreased the secretions of IL-6 and MCP-1 induced by CRP. Moreover, 10 micromol/L of atorvastatin completely abrogated CRP-induced increase in IL-6 and MCP-1 by attenuating the activation of NF-kappaB. The present study demonstrated that inhibiting effect of atorvastatin on CRP-induced inflammatory response in cultured PASMCs was associated with NF-kappaB pathway. This pathway might represent a promising target for controlling CRP-induced inflammatory response in pulmonary arterial diseases.
Cardiovascular therapeutics 2010
BACKGROUND:Muscle fibers overlying the intramyocardial segment of an epicardial coronary artery are termed myocardial bridging (MB). Variable prevalence of MB has been described at autopsy and angiographic series with small and large sample size studies. In addition, no similar study was reported in Chinese population. The aim of this study was to investigate the angiographic prevalence of MB in consecutive 37,106 Chinese patients with chest pain from our center.METHODS:We conducted an observational study to evaluate the consecutive cases with MB among patients undergone selective coronary angiography, and analyzed the angiograhic prevalence and clinical features of MB in this study of very large sample size.RESULTS:Among 37 105 patients with chest pain we found 1002 cases with 1011 MBs in a retrospective manner, and the overall prevalence was 2.70%. Although more than 99% (991/1002) of patients had single bridge, 8 cases were found to have more than two MBs (seven with two, and one with three). Altogether 54.39% of cases (545/1002) had MB without atherosclerotic lesions, and 96.24% (973/1011) of bridging located in the left anterior descending coronary artery (LAD), mainly in the middle of LAD (792/1011, 78.33%). According to Nobel classification, of the single bridge (n=991), <50% of obstruction was predominant (471/991, 47.52%). Totally 50%-69% accounted for 34.81% (345/991), >70% of obstruction was 17.65% (175/991).CONCLUSIONS:These data showed that the prevalence of angiographically detectable MB in Chinese patients with chest pain was similar to those of the previous studies, with 2.7% prevalence in this very large sample size.
Chinese medical journal 2008
BACKGROUND:Emerging data suggest that inflammation may play an important role in the pathogenesis of coronary artery disease. However, the relation of inflammatory status to coronary vasospasm has been less investigated in patients with variant angina (VA).PURPOSE:The aim of this study, therefore, was to determine peripheral circulating white blood cells as well as monocyte cells and plasma C-reactive protein (CRP) and interleukin-6 (IL-6) levels in patients with VA, and to compare patients with VA, stable coronary artery disease, and controls with angiographically normal coronary arteries.METHOD:Thirty-three consecutive patients with documented VA, 26 with stable coronary artery disease, and 22 normal controls (with angiographically normal coronary arteries) were involved in this study. The peripheral blood was taken, and white blood cells and monocyte cells were counted. The plasma concentrations of CRP and IL-6 were also evaluated by enzyme-linked immunosorbent assay (ELISA).RESULTS:The data showed that white blood cell counts and monocyte cell counts were significantly higher in patients of the VA group than in the other two groups (white blood cell counts: 7340+/-1893/mm vs. 6187+/-1748/mm vs. 5244+/-1532/mm, P<0.05, respectively; monocyte cell counts: 510+/-213/mm vs. 425+/-209/mm vs. 383+/-192/mm, P<0.05, respectively). Similarly, levels of plasma CRP and IL-6 were also significantly higher in patients of the VA group than in patients with stable coronary artery disease (CRP: 0.42+/-0.21 mg/l vs. 0.27+/-0.14 mg/l; IL-6: 10.4+/-1.0 pg/dl vs. 6.2+/-0.7 pg/dl, P<0.01, respectively), and patients with normal controls (CRP: 0.42+/-0.21 mg/l vs. 0.17+/-0.10 mg/l; IL-6: 10.4+/-1.0 pd/dl vs. 3.0+/-0.7 pg/dl, P<0.01, respectively). The multivariate analysis showed that CRP was the independent variable most strongly associated with VA.CONCLUSION:Taken together, these findings suggested that more chronic, severe inflammation might be involved in the pathogenesis of VA, manifested by increased counts of circulating inflammatory cells and elevated plasma levels of CRP and IL-6.
Coronary artery disease 2008
BACKGROUND:Slow coronary filling of epicardial coronary arteries in the absence of stenosis is not infrequently detected finding during routine coronary angiography. There is mounting evidence suggested that an inflammatory process play an important role in atherosclerotic pathogenesis appeared in different clinical settings. However, the possible association between inflammation and slow coronary flow (SCF) has not been investigated. We examined whether the increased inflammatory markers are present in patients with SCF.METHODS:Forty-two patients with SCF detected by coronary angiography via the Thrombosis In Myocardial Infarction (TIMI) frame count method were enrolled in this study. The plasma concentration of high-sensitivity C-reactive protein (CRP) and interleukin-6 (IL-6) were evaluated using commercial available kits. Data were compared with 30 control subjects with angiographically normal coronary flow.RESULTS:There are no differences regarding clinical characteristics between the 2 groups. The data showed, however, that plasma CRP and IL-6 concentrations were higher in patients with SCF compared with normal control subject (CRP: 0.27 +/- 0.16 vs. 0.22 +/- 0.11mg/l; and IL-6: 8.7 +/- 0.8 vs. 5.4 +/- 0.4pg/ml, p < 0.01 respectively). In addition, mean TIMI frame count was positively correlated with plasma CRP and IL-6 concentrations (CRP: gamma = 0.551; IL-6: gamma = 0.573, p < 0.01 respectively).CONCLUSIONS:Plasma concentration of CRP and IL-6 concentrations increased, and was positive correlated with TIMI frame count in patients with SCF compared with normal coronary flow subject. Therefore, whether the increased inflammatory markers are related to the pathogenesis of SCF in these patients deserved further investigation.
Clinica chimica acta; international journal of clinical chemistry 2007
Coronary artery ectasia (CAE) is well-recognized, angiographic finding of abnormal coronary dilatation, and detected in 0.3-5.3% of angiographic studies. The gold standard for diagnosis this type of aneurysm is coronary angiography, which provides information about the size, sample, location and number of aneurysms. Despite growing prevalence in recent years, controversy still exists as to the pathogenetic mechanisms that underlie this entity. An increased incidence of CAE has been reported in several disorders. Examples include atherosclerotic vascular disease, heterozygous familial hypercholesterolemia, usage of substances including herbicide spray, acetylcholinesterase inhibitors and nitrates, previous arterial balloon angioplasty, polyarteritis nodosa and Kawasaki syndrome. In addition, possible factors contributing to CAE are imbalance between matrix metalloproteinase and tissue inhibitor of metalloproteinase, angiotensin converting enzyme genotype, elevated homocysteine levels, cocaine user, smoking, vascular trauma, nitrate use and diabetes. Emerging investigations have pinpointed inflammation as a central process in all stages of atherosclerosis. This inflammatory process culminates in acute thrombotic complications and clinical events, which is involved in different clinical settings of atherosclerotic diseases. Recent data have also showed that CAE is associated with inflammatory response presented as elevated inflammatory cytokines and C-reactive protein. Accordingly, more complete understanding of the pro- and anti-inflammatory circuits that operate during CAE in particular may foster the development of novel therapeutic approaches.
Medical hypotheses 2007
BACKGROUND:The pathophysiological mechanism in cardiac syndrome X has been suggested as impairment in normal endothelial function of the coronary microvasculature, resulting in inadequate flow reserve. However, despite the extensive studies, the precise mechanisms in cardiac syndrome X remain unclear.PURPOSE:The present study was, therefore, to investigate whether inflammatory cells and markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) might be involved in the pathogenesis of cardiac syndrome X.METHODS:Thirty-six female patients with cardiac syndrome X and 30 sex-matched normal controls were prospectively enrolled in this study. Blood samples were drawn for measuring white blood and monocyte cells, inflammatory markers such as CRP and IL-6, and data were compared between patients with cardiac syndrome X and normal controls.RESULTS:The data showed that increased numbers of white blood and monocyte cells were found in patients with cardiac syndrome X compared with normal controls (white blood cells: 7072+/-1146/mm(3) vs. 6138+/-1079/mm(3); monocyte cells: 612+/-186/mm(3) vs. 539+/-190/mm(3)p<0.05, respectively). Moreover, patients with cardiac syndrome X were detected to have significantly higher plasma CRP and IL-6 levels in comparison with patients with normal controls (CRP: 0.48+/-0.26 mg/L vs. 0.22+/-0.15 mg/L; IL-6: 13.4+/-1.2 pg/dl vs. 6.2+/-0.6 pg/dl, p<0.01, respectively). The multivariate analysis showed that CRP was the independent variable most strongly associated with cardiac syndrome X.CONCLUSIONS:Our data suggested that low-grade, chronic inflammation might contribute to the development of cardiac syndrome X manifested by increased plasma levels of inflammatory cells and inflammatory markers.
Cytokine 2007
The phenomenon of slow progression of angiographic contrast in the coronary arteries in the absence of stenosis in the epicardial vessels in some patients presenting with chest pain has been recently called as slow coronary flow syndrome because the underlying pathophysiological mechanisms as well as therapeutics of this unique phenomenon is less well understood. Although this phenomenon was first reported on in 1972 by Tambe, few studies have focused on the etiology of this unique angiographic finding since that time. Several hypotheses have been poised to elucidate this phenomenon, including a form of early phase of atherosclerosis, small vessel dysfunction, Hagen-Poiseuille's equation model, imbalance between vasoconstrictor and vasodilatory factors, and platelet function disorder. During the last several years there has been arisen the most interesting concept of "atherosclerosis as a inflammation disease", which is involving the different entities of coronary artery disease covering slow coronary flow syndrome. The angiographic finding appeared as slow flow is an important clinical entity because it may be the cause of angina at rest or during exercise, acute myocardial infarction, and hypertension. Despite the good prognosis, patients complained commonly of persistent uncomfortable chest, which can significantly impair quality of life. There is no effective therapy for patients with slow coronary flow syndrome up to now. Statins have been showed the important benefits for the large populations of individuals at high risk of coronary artery disease. In addition to lowering lipid profile, statins have pleiotropic effects on improving vascular function. Increasing evidence, suggests that reduction of cardiovascular events conferred by statins relates not only to cholesterol lowering but also to direct effects on endothelium function as well as anti-thrombotic and anti-inflammatory actions. Accordingly, we hypotheses that these pleiotropic effects of statin may be beneficial for patients with slow coronary flow syndrome due to its pharmacological basis.
Medical hypotheses 2007
The development of coronary stent has revolutionized the field of interventional cardiology by reducing the incidence of restenosis after balloon angioplasty. However, the stent has still associated with a serious complication, namely, in-stent restenosis. Although, restenosis following coronary stenting has long been attributed to neointimal proliferation, thrombosis, and negative remodeling, the inflammation may be a trigger for those vascular reactions following coronary stenting. Both experimental and clinical studies have demonstrated a marked activation of local and systemic inflammatory response following stent implantation, suggesting that inflammation may play an important role in determining in-stent restenosis via neointimal proliferation. The key role of inflammation in vascular healing and in-stent retsenosis has also been increasingly well understood. Recently, drug-eluting stents (DESs) have been shown to decrease in-stent restenosis in a large number of clinical studies. In addition to their anti-proliferative activity, DESs have been considered to possess an anti-inflammatory property, especially for sirolimus-eluting stent compared with bare metal stent. Moreover, the benefit of the anti-inflammatory therapy during the peri-procedural period and long-term follow-up by means of drug administration is also dependent on the inflammatory status during percutaneous coronary intervention. Measurement of cytokine and acute phase proteins, such as C-reactive protein, therefore, may be important to identify high-risk subjects and develop specific treatment tailored to the individual patients with stent restenosis. Thus, therapeutic approach should be further directed toward increasing local resistance to proliferative inflammatory stimuli by means of anti-proliferative, locally delivered drugs and reducing the magnitude and persistence of systemic inflammation.
Medical hypotheses 2007
Peripheral arterial disease (PAD) includes a wide range of manifestations in the lower limb, from asymptomatic to symptomatic disease ranging from intermittent claudication to critical limb ischemia, with ulcers, rest pain, or gangrene. It is manifestation of generalized atherosclerosis and this is clearly shown by the high prevalence of coexistence coronary and cerebral arterial disease in these patients. The cumulative findings on molecular and cellular biology have dramatically changed our concept of atherosclerotic disease. Recently, it has become clear that inflammation is fundamental to the process of atherosclerosis. Although the relation between inflammation and PAD is not well characterized, the emerging data demonstrated that PAD is a common manifestation of atherosclerosis that is associated with a systemic inflammation. The most important risk factors for PAD are similar to those of atherosclerotic disease elsewhere: age, male sex, diabetes mellitus, smoking, hypertension, hyperlipidemia, and hereditary factors. Serum levels of inflammatory markers, especially after exercise, have been found to be higher in patients with PAD than in controls, and associated with prognosis as well as restenosis in patients with PAD after revascularization. In the general United States adult population, inflammation is independently associated with PAD in a cross-sectional, nationally large representative sample. All of those evidences indicate that PAD is one aspect of atherosclerosis, a disease rationally connects with inflammation, which may further change our preventive and therapeutic strategies.
Medical hypotheses 2007
