C-reactive protein: linking inflammation to cardiovascular complications.
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C-Reactive Protein↗
Biomedical subjects
V Pasceri
Publications and source records attributed to V Pasceri.
Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs.
BACKGROUND: C-reactive protein (CRP) induces adhesion molecule expression by endothelial cells. However, the effects of CRP on chemokine expression by endothelial cells are not known. METHODS AND RESULTS: We tested the effects of CRP on the production of the chemokines monocyte chemoattractant protein-1 (MCP-1) and RANTES in cultured human umbilical vein endothelial cells. The secretion of chemokines was assessed by ELISA. Incubation with 100 microgram/mL recombinant human CRP induced a 7-fold increase in MCP-1 but no change in RANTES secretion. We showed that the effect of CRP on MCP-1 was present even at 5 microgram/mL CRP, with stepwise increases as the CRP concentration was increased to 10, 50, and 100 microgram/mL. The effect of CRP on MCP-1 induction was not influenced by aspirin (at concentrations up to 1 mmol/L), but it was significantly inhibited by 5 micromol/L simvastatin. The peroxisome proliferator-activated receptor-alpha activators fenofibrate (100 micromol/L) and Wy-14649 (100 micromol/L) almost completely abolished the induction of MCP-1, but the peroxisome proliferator-activated receptor-gamma activator ciglitazone had only a moderate effect. CONCLUSIONS: These results further strengthen the role of CRP in the pathogenesis of vascular inflammation and, likely, atherosclerosis and provide a crucial insight into a novel mechanism of action of anti-atherosclerosis drugs such as simvastatin and fenofibrate.
C-Reactive Protein↗
Direct proinflammatory effect of C-reactive protein on human endothelial cells.
BACKGROUND: The acute-phase reactant C-reactive protein (CRP) is an important risk factor for coronary heart disease. However, the possible effects of CRP on vascular cells are not known. METHODS AND RESULTS: We tested the effects of CRP on expression of adhesion molecules in both human umbilical vein and coronary artery endothelial cells. Expression of vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM-1), and E-selectin was assessed by flow cytometry. Incubation with recombinant human CRP (10 microg/mL) for 24 hours induced an approximately 10-fold increase in expression of ICAM-1 and a significant expression of VCAM-1, whereas a 6-hour incubation induced significant E-selectin expression. Adhesion molecule induction was similar to that observed in endothelial cells activated with interleukin-1beta. In coronary artery endothelial cells, induction of ICAM-1 and VCAM-1 was already present at 5 microg/mL and reached a maximum at 50 microg/mL, at which point a substantial increase in expression of E-selectin was also evident. The CRP effect was dependent on presence of human serum in the culture medium, because no effect was seen in cells cultured with serum-free medium. In contrast, interleukin-1beta was able to induce adhesion molecule expression in the absence of human serum. CONCLUSIONS: CRP induces adhesion molecule expression in human endothelial cells in the presence of serum. These findings support the hypothesis that CRP may play a direct role in promoting the inflammatory component of atherosclerosis and present a potential target for the treatment of atherosclerosis.
Arteriosclerosis↗
Modulation of vascular inflammation in vitro and in vivo by peroxisome proliferator-activated receptor-gamma activators.
BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPARgamma) is expressed in atherosclerotic plaques and in endothelial cells. The possible effects of PPARgamma activators on endothelial activation and inflammatory response within the plaque are currently unknown. METHODS AND RESULTS: We tested the hypothesis that PPARgamma activators inhibit vascular cell adhesion molecule (VCAM-1) and intercellular adhesion molecule (ICAM-1) expression in cultured endothelial cells (evaluated by flow cytometry) and homing of monocyte/macrophages to atherosclerotic plaques in vivo. In endothelial cells, the PPARgamma agonists troglitazone at 100 micromol/L and 15-deoxy-(Delta12,14)-prostaglandin J(2) (15d-PGJ2) at 20 micromol/L markedly attenuated the tumor necrosis factor-induced expression of VCAM-1 and ICAM-1. A significant inhibition of VCAM-1 expression was also evident at 5 and 10 micromol/L 15d-PGJ2 and 20 micromol/L troglitazone. Expression of E-selectin and PECAM-1 was not altered. To confirm the biological relevance of these results, we assessed the effects of troglitazone on monocyte/macrophage homing to atherosclerotic plaques in apoE-deficient mice. A 7-day treatment with troglitazone (400 mg/kg) significantly reduced monocyte/macrophage homing to atherosclerotic plaques (236+/-77 versus 177+/-43 macrophages, P=0.03); an even more striking inhibition was found at 3200 mg/kg troglitazone (344+/-76 versus 172+/-83 macrophages, P=0.005). CONCLUSIONS: PPARgamma activators inhibit expression of VCAM-1 and ICAM-1 in activated endothelial cells and significantly reduce monocyte/macrophage homing to atherosclerotic plaques. These findings suggest that PPARgamma activators, currently used in treatment of type II diabetes, may have beneficial effects in modulating inflammatory response in atherosclerosis.
Animals↗
Is there an antigenic mimicry between arteriosclerotic lesions and H. pylori antigens?
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Aged↗
A tale of two diseases: atherosclerosis and rheumatoid arthritis.
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Angina, Unstable↗
Effects of atrial pacing on arterial and coronary sinus endothelin-1 levels in syndrome X.
Syndrome X may be caused by a coronary microvascular dysfunction, possibly due to abnormalities in coronary endothelial function. Previous studies suggested that endothelin-1 (ET-1) might be involved in the pathogenesis of syndrome X. Baseline arterial and coronary sinus ET-1 levels were measured in 13 patients with syndrome X (10 women, 52+/-7 years) and in 8 control patients (5 women, 46+/-11 years). ET-1 was also measured after atrial pacing in 12 patients with syndrome X and all controls. To simultaneously assess the activity of nitric oxide, guanosine 3'-5'-cyclic monophosphate (cGMP) was also measured in 11 patients with syndrome X and 7 controls. Baseline arterial (2.27+/-0.46 vs. 1.90+/-0.22 pg/ml, p<0.05) and coronary sinus (2.03+/-0.43 vs. 1.68+/-0.28 pg/ml, p = 0.06) ET-1 plasma levels were higher in patients than in controls. After pacing, arterial ET-1 levels did not change in either group and coronary sinus ET-1 levels were also unchanged in controls. In contrast, coronary sinus ET-increased significantly in response to atrial pacing in patients with syndrome X (p = 0.023), and differences between coronary sinus ET-1 levels of patients with syndrome X and controls after pacing became highly significant (2.22+/-0.45 vs. 1.69+/-0.20 pg/ml, respectively, p = 0.006). No significant differences in arterial and coronary sinus cGMP concentrations were found between the 2 groups, both at baseline and after pacing. Our findings suggest that an increased vasoconstrictor activity of microvascular endothelium is present in at least some patients with syndrome X and may be involved in the pathogenesis of the syndrome.
Adult↗
Atenolol versus amlodipine versus isosorbide-5-mononitrate on anginal symptoms in syndrome X.
The effects of a beta blocker (atenolol), a calcium antagonist (amlodipine), and a nitrate (isosorbide-5-mononitrate) on anginal symptoms in 10 patients with syndrome X were assessed in a crossover, double-blind, randomized trial. Only atenolol was found to significantly improve chest pain episodes, suggesting that it should be the preferred drug when starting pharmacologic treatment of patients with syndrome X.
Adrenergic beta-Antagonists↗
Progress in the molecular diagnosis of facioscapulohumeral muscular dystrophy and correlation between the number of KpnI repeats at the 4q35 locus and clinical phenotype.
Genotype analysis by using the p13E-11 probe and other 4q35 polymorphic markers was performed in 122 Italian facioscapulohumeral muscular dystrophy families and 230 normal controls. EcoRI-BlnI double digestion was routinely used to avoid the interference of small EcoRI fragments of 10qter origin that were found in 15% of the controls. An EcoRI fragment ranging between 10 and 28 kb that was resistant to BlnI digestion was detected in 114 of 122 families (93%) comprising 76 familial and 38 isolated cases. Among the unaffected individuals, 3 were somatic mosaics and 7, carrying an EcoRI fragment larger than 20 kb, could be rated as nonpenetrant gene carriers. In a cohort of 165 patients with facioscapulohumeral muscular dystrophy we found an inverse correlation between fragment size and clinical severity. A severe lower limb involvement was observed in 100% of patients with an EcoRI fragment size of 10 to 13 kb (1-2 KpnI repeats left), in 53% of patients with a fragment size of 16 to 20 kb (3-4 KpnI repeats left), and in 19% of patients with a fragment size larger than 21 kb (>4 KpnI repeats left). Our results confirm that the size of the fragment is a major factor in determining the facioscapulohumeral muscular dystrophy phenotype and that it has an impact on clinical prognosis and genetic counseling of the disease.
Adult↗
Homocysteine and coronary heart disease: a review of the current evidence.
The high frequency of premature atherosclerosis in patients with homocystinuria suggested the hypothesis of an association between hyperhomocysteinemia and coronary heart disease. Experimental studies have shown that severe homocysteinemia has toxic effects on the endothelium and may alter haemostatic balance. Although case controls studies have suggested a significant association between mild hyperhomocyst(e)inemia and coronary heart disease, prospective studies have not completely confirmed these findings. Results from the ongoing randomized trials will help determine whether reduction of homocysteine levels will be associated with a reduction of cardiac events and possibly mortality in patients.
Animals↗
Circadian distribution of ischemic attacks and ischemia-related ventricular arrhythmias in patients with variant angina.
BACKGROUND: There are limited data about the circadian distribution of ischemic episodes in patients with variant angina. Furthermore, no previous study investigated whether ischemia-related ventricular arrhythmias follow a circadian variation in these patients. METHODS: The circadian variation of transient ischemia and ischemia-induced ventricular arrhythmias was assessed by cosinor methodology on 24-hour Holter recordings of 26 patients with variant angina. RESULTS: On the whole, 301 ischemic episodes were detected in the population, with premature ventricular complexes occurring in 49 of them (16%). Ischemic episodes followed a typical circadian variation (acrophase hr 02:36, p < 0.01) in the total sample. However, a significant circadian variation of ischemic episodes was detectable in the 14 patients without (n = 167, acrophase hr 04:00, p < 0.0001), but not in the 12 patients with (n = 134, p = 0.14) hemodynamically significant coronary stenoses, independently of the location (anterior/inferior) of ischemia. There was no significant circadian variation of ischemia-related ventricular arrhythmias. CONCLUSIONS: Among patients with variant angina, a clearcut circadian variation of ischemia is present in those without, but not in those with, hemodynamically significant coronary artery stenoses, thus suggesting that different pathophysiologic mechanisms may operate, at least in part, in triggering coronary spasm in these two subgroups of patients. There was no significant circadian variation of ischemia-related ventricular arrhythmias in these patients.
Angina Pectoris, Variant↗
Prognostic role of heart rate variability in patients with a recent acute myocardial infarction.
A low heart rate variability (HRV) has been shown to be a powerful predictor of cardiac events in patients surviving an acute myocardial infarction (MI), but it is not clear yet which among the HRV parameters has the best predictive value. Time domain and frequency domain HRV was assessed on 24-hour predischarge Holter recording of 239 patients with a recent MI. Patients were followed up for 6 to 54 months (median 28), during which 26 deaths (11%) occurred, 19 of which were cardiac in origin and 12 were sudden. Most HRVs did not show any difference between patients with or without mortality end points, but the average low-frequency and low-frequency/high-frequency ratio was lower in patients with events. However, when dichotomized according to cut points that maximized the risk of sudden death, several HRVs were significantly predictive of clinical end points. Overall, the mean of the standard deviations of all RR intervals for all 5-minute segments and the standard deviation of the mean RR intervals for all 5-minute segments were the time domain variables most significantly associated with mortality end points, whereas very low frequency was the most predictive frequency domain variable. Compared with the best time domain variables, very low frequency showed a better sensitivity (0.27 to 0.42 vs 0.19 to 0.33) for end points with only a small loss in specificity (0.92 vs 0.96). On multivariate Cox proportional analysis, a left ventricular ejection fraction <40% and a number of ventricular premature beats > or = 10/hour were the most powerful independent predictors for all end points, whereas no HRV was independently associated with the events. A low frequency/high frequency ratio < 1.05 only had a borderline association with sudden death (RR = 2.86, p = 0.076). Our data show a strong association between HRV and mortality in patients surviving a recent MI, with a slight better sensitivity of frequency domain analysis. In our study, however, HRV did not add independent prognostic information to more classic prognostic variables (e.g., left ventricular function and ventricular arrhythmias).
Aged↗
Association of virulent Helicobacter pylori strains with ischemic heart disease.
BACKGROUND: Previous studies have reported an association between chronic Helicobacter pylori infection and ischemic heart disease. However, it is not clear whether this association is really due to the virulence of the bacterium or is merely the result of confounding factors (in particular, age and social class). METHODS AND RESULTS: We assessed the prevalence of infection by Helicobacter pylori and by strains bearing the cytotoxin-associated gene-A (CagA), a strong virulence factor, in 88 patients with ischemic heart disease (age, 57+/-8 years; 74 men) and in 88 age- and sex-matched controls (age, 57+/-8 years; 74 men) with similar social background. Prevalence of Helicobacter infection was significantly higher in patients than in controls (62% versus 40%; P=.004), with an odds ratio of 2.8 (95% CI, 1.3 to 7.4; P<.001) adjusted for age, sex, main cardiovascular risk factors, and social class. Patients with ischemic heart disease also had a higher prevalence of CagA-positive strains (43% versus 17%; P=.0002), with an adjusted odds ratio of 3.8 (95% CI, 1.6 to 9.1; P<.001). Conversely, prevalence of CagA-negative strains was similar in patients and controls (19% versus 23%), with an adjusted odds ratio of 0.8 (95% CI, 0.4 to 1.4). CONCLUSIONS: The association between Helicobacter pylori and ischemic heart disease seems to be due to a higher prevalence of more virulent Helicobacter strains in patients. These results support the hypothesis that Helicobacter pylori may influence atherogenesis through low-grade, persistent inflammatory stimulation.
Aged↗
Role of abnormal pain sensitivity and behavioral factors in determining chest pain in syndrome X.
OBJECTIVES: We sought to investigate whether patients with syndrome X have an abnormal perception of cardiac pain. BACKGROUND: Previous studies have reported an increased sensitivity to potentially painful cardiac stimuli in patients with syndrome X. However, it is not clear whether this increase is due to an increased perception of pain or to an enhanced tendency to complain. METHODS: We assessed cardiac sensitivity to pain in 16 patients with syndrome X and 15 control subjects by performing right atrial and ventricular pacing with increasing stimulus intensity (1 to 10 mA) at a rate 5 to 10 beats higher than the patient's heart rate. False and true pacing were performed in random sequence, with both patients and investigators having no knowledge of the type of stimulation being administered. RESULTS: No control subject had pacing-induced pain; conversely, 8 patients with syndrome X reported angina during atrial pacing (50%, p < 0.01) and 15 during ventricular pacing (94%, p < 0.001). During atrial stimulation, both true and false pacing caused chest pain in a similar proportion of patients (50% vs. 63%, p = 0.61), whereas during ventricular stimulation, true pacing caused chest pain in a higher proportion of patients (94% vs. 50%, p < 0.05). Pain threshold and severity of pain (1 to 10 scale) were similar during true and false atrial pacing, whereas true ventricular pacing resulted in a lower pain threshold (mean +/- SD 3.7 +/- 3.0 vs. 7.9 +/- 2.8 mA, p < 0.001) and a higher level of pain severity (7.3 +/- 2.7 vs. 3.1 +/- 3.5, p < 0.001) than did false pacing. CONCLUSIONS: Patients with syndrome X frequently reported chest pain even in the absence of cardiac stimulation. Yet, in addition to this increased tendency to complain, they also exhibited a selective enhancement of ventricular painful sensitivity to electrical stimulation.
Adult↗
Role of different determinants of psychological distress in acute coronary syndromes.
OBJECTIVES: The aim of this study was to examine the prevalence of psychological distress and of its major determinants in acute coronary patients and in a control group. BACKGROUND: The prevalence and major determinants of psychological distress in acute coronary patients are not clear. METHODS: One hundred and thirty cardiac patients (110 men, age 56+/-9; 85 with acute myocardial infarction and 45 with unstable angina) and 102 controls hospitalized for acute trauma (70 men, age 55+/-9 years) were studied and the level of psychological distress estimated by a Modified Maastricht Questionnaire, self-ratings and ratings by a close relative. Major determinants of psychological distress were assessed by the Life Events Assessment, the Social Support Questionnaire and the Ways of Coping Checklist. RESULTS: The average level of psychological distress was significantly higher (p < 0.001) in coronary patients than in controls in all tests (self-evaluation=7.1+/-2.3 vs 4.3+/-2.4; relative-evaluation = 7.4+/-2.4 vs 4.2+/- 2.5; Modified Maastricht Questionnaire=91+/-32 vs 59+/-30). Cardiac patients reported significantly higher (p < 0.05) levels of social isolation (28.9+/-11.1 vs 23.4+/-8.8), self-blame (7.2+/-1.9 vs 5.8+/- 1.6) and avoidance (21.1+/-3.5 vs 18.9+/-3) and more painful life events (3.9+/-3.8 vs 2.6+/-2.2), than controls. However, not all patients had evidence of distress; indeed, cluster analysis identified a subgroup that comprised 75% of controls and 25% of cardiac patients with no determinants eliciting distress, while the other four subgroups, with one or more determinants of distress, comprised about 75% of patients and only 25% of controls. CONCLUSIONS: These results show that a high level of psychological distress is detectable in about 75% of patients with acute myocardial infarction or unstable angina and is related to one or more major determinants.
Adaptation, Psychological↗
Helicobacter pylori infection and ischaemic heart disease.
Helicobacter pylori infection is probably one of the most widely spread infectious diseases in man and a growing body of knowledge provides evidence in favour of a causal link between this infection and the majority of upper gastrointestinal conditions. For example, we now know that peptic ulcer disease is an infectious disease; if the infection is diagnosed and treated, ulcer can be cured. On the other hand, in recent years, a number of epidemiological studies have focused on the possible relation between ischaemic heart disease and several infectious disorders, such as chronic dental infections, Cytomegalovirus, Coxsackie viruses, Chlamydia and, finally Helicobacter pylori. The results of studies on the association between ischaemic heart disease and Helicobacter pylori have, in particular, often been contradictory, and only some studies adjusted the results for confounding factors, and the adjustment of the results in some cases modified the association. In conclusion, even if coronary atherosclerosis may now be considered as an inflammatory process, according to several histologic and pathophysiologic studies, we cannot, for the moment, be sure that it is an infectious disease.
Antigens, Bacterial↗
Changing features of anginal pain after PTCA suggest a stenosis on a different artery rather than restenosis.
BACKGROUND: We recently found that patients who had had two myocardial infarctions in different myocardial regions frequently reported different locations of infarct pain, whereas patients who had had two infarcts at the same site had a similar distribution of pain. The aim of this study was to assess whether a different location of anginal pain may help identify patients with a new stenosis on an artery perfusing another myocardial region as opposed to those with restenosis after coronary angioplasty (PTCA). METHODS AND RESULTS: We studied 38 patients (59+/-11 years old) who underwent PTCA for single-vessel disease, with recurrence of symptoms requiring repeat coronary angiography during a 3-year follow-up. According to our inclusion criteria, angiography showed either a significant restenosis of the dilated lesion, with no evidence of lesions in the other vessels (n=26), or a new stenosis in either of the other coronary arteries, with no restenosis in the dilated vessel (n= 12). Before each procedure, patients reported the location and radiation of anginal pain. There was no relation between location of pain and site of the coronary stenosis. However, none of the patients with restenosis reported a different location of pain after angioplasty, compared with 5 patients with new stenosis (0% versus 42%, P=.002). Radiation of pain involved different areas of the body in 1 patient with restenosis and in 6 with new stenosis (4% versus 50%, P=.002). Overall, location or radiation of pain in a different body area had a specificity of 96% and a sensitivity of 58% in detecting a stenosis on a new artery. CONCLUSIONS: A different location of anginal pain may distinguish patients with a new coronary stenosis from those with restenosis after PTCA for single-vessel disease. These findings suggest that in individual patients, differences in the location of cardiac pain may be indicative of the occurrence of ischemia in different myocardial regions.
Aged↗
Primary coronary angioplasty versus thrombolysis.
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Angioplasty, Balloon, Coronary↗