Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atherosclerosis has long been recognised as having an inflammatory component, and this has a particularly important bearing on to its clinical complications as it may result in plaque instability. Results of recent epidemiological studies have reinforced the potential importance of this aspect of the disease. Positive associations have been reported between exposure to several specific pathogens, and future risk of coronary heart disease (CHD). Whilst it is possible that each individual organism contributes to this susceptibility by a different mechanism, it is more likely that one or more common mechanism(s) exist. One possible hypothesis is that an immune response mounted against antigens on pathogenic organisms cross-react with homologous host proteins in a form of 'molecular mimicry'. A group of protein candidates that may be implicated in this process are the stress-induced proteins collectively known as heat shock proteins (HSP). HSPs are expressed and/or secreted by several pathogens, principally Chlamydia pneumoniae and Helicobacter pylori, but are also elaborated by mammalian vascular cells exposed to the stress associated with reperfusion injury or acute hypertension. The HSPs are also expressed by cells within atherosclerotic plaques. Serum titres of anti-HSP antibodies have been reported to be positively related to future risk of CHD. In addition, purified anti-HSP antibodies recognise and mediate the lysis of stressed human endothelial cells and macrophages in vitro. Furthermore, immunisation with HSP exacerbates atherosclerosis in experimental animal models. Some human vaccines, such as BCG, contain HSPs, hence although vaccination programmes are vital for maintaining 'herd' immunity and the prevention of serious infectious disease, they may leave a legacy of increased susceptibility to atherosclerosis. Development of HSP-free vaccines could satisfy the twin goals of protection from infection and reduced incidence of coronary disease.
 ...
PMID:Molecular mimicry in atherosclerosis: a role for heat shock proteins in immunisation. 1470 75

Previous studies have linked essential sustained hypertension with Chlamydia pneumoniae (C. pneumoniae) and changes in intima-media thickness (IMT) of carotid arteries. The aim of this study was to examine if similar associations exist in subjects with white-coat hypertension. C. pneumoniae IgA and IgG antibody titers were measured in 125 patients with white-coat hypertension and 54 normotensives. All participants underwent a 24 h ambulatory blood pressure (BP) monitoring, clinic BP readings and common-internal carotid artery IMT measurements. Seventy subjects of the white-coat group (56%) and 15 of the control group (27.8%) had IgG titers >/=80 (crosstabs; P<0.001). IgA titers were elevated in 75 subjects of the white-coat group (60%) and 10 (18.5%) of the control group (crosstabs; P<0.001). The IMT of the carotid arteries in the white-coat group was significantly higher than that of the normotensive group (t-test; P<0.001 and P<0.001, respectively). In contrast, carotid IMT did not differ between C. pneumoniae-seropositive and C. pneumoniae-seronegative groups concerning both IgG and IgA antibody titers. Our findings suggest that both C. pneumoniae antibody titers and carotid IMT were increased in subjects with white-coat hypertension. The preceding associations strengthen prior evidence in favor of the opinion that white-coat hypertension is not an innocent phenomenon.
 ...
PMID:High prevalence of Chlamydia pneumoniae antibodies in white-coat hypertensives. 1281 5

Chlamydia pneumoniae (Cpn) has been associated with human coronary artery disease but causal relevance as a risk factor has not been shown. Several rabbit and mouse model studies demonstrate exacerbation of aortic atherosclerosis by Cpn, however impact of Cpn on coronary artery disease (CAD) and survival outcomes has not been shown. To study this, we used specific pathogen-free, inbred, transgenic-CAD Dahl salt-sensitive (S) hypertensive (Tg53) rats and control inbred, non-transgenic Dahl S (nonTg) rats to analyze the effects of Cpn infection on macrophage foam cell formation, coronary artery disease progression, and effect on survival. Cpn infection induced acceleration of foam cell formation in hyperlipidemic Tg53 recruited peritoneal macrophages. This effect is hyperlipidemia-dependent. The transcription profile of Tg53-Cpn macrophage foam cells is different from control mock-inoculated (Tg53-spg) and heat-inactivated (Tg53-iCpn) macrophages (ANOVA P < 0.0001). Decreased survival was detected in Tg53-Cpn compared with control nonTg-Cpn and mock-infected Tg53-mouse pneumonitic rats (P = 0.009) and was associated with "culprit" coronary plaques and left atrial thrombi. These data demonstrate that in the presence of significant hyperlipidemia and hypertension, one-time Cpn infection at 5 mo of age (associated with early CAD stage) accelerates progression to overt-CAD in the Tg53 rat model. The data support the hypothesis that untreated Cpn infection is a causal risk factor for CAD progression most likely mediated by Cpn-induced accelerated macrophage foam cell formation.
 ...
PMID:Chlamydia pneumoniae accelerates coronary artery disease progression in transgenic hyperlipidemia-genetic hypertension rat model. 1457 21

Infection with Chlamydia pneumoniae has been suggested to play a role in the development and maintenance of atherosclerosis based on differences in the prevalence of antibodies against Chlamydia pneumoniae in patients with and without atherosclerotic lesions. We evaluated the prevalence of Chlamydia pneumoniae DNA in the white cells of the peripheral blood in 194 patients with diabetes mellitus, 50 patients with acute coronary syndrome, 102 hypertensive patients, 193 patients having suffered a stroke and in 368 healthy subjects with a nested polymerase chain reaction (nPCR). Overall the prevalence of Chlamydia pneumoniae DNA in peripheral blood cells was: diabetes mellitus (11.9%), stroke (10.4%), hypertension (6.9%), acute coronary syndrome (4.0%) and healthy subjects (7.9%). The prevalence of Chlamydia pneumoniae DNA in the patients was not significantly different from prevalence in the healthy subjects. However, a significant association was found between high levels of triglycerides and presence of C. pneumoniae DNA (OR = 3.27, p < 0.04). The prevalence of C. pneumoniae DNA was not associated with age, gender, smoking, BMI, HDL, CRP, plasma creatinine and symptoms or signs of ischaemic heart disease. The association between high levels of triglycerides and C. pneumoniae DNA suggests that infection by C. pneumoniae affects lipid metabolism.
 ...
PMID:Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in healthy control subjects and patients with diabetes mellitus, acute coronary syndrome, stroke, and arterial hypertension. 1460 8

Stroke is a disease with well-defined modifiable risk factors such as arterial hypertension, smoking, diabetes, hyperlipidemia and atrial fibrillation. The need of new risk factors is based on the fact that only half the cardiovascular disease risk is explained by conventional risk factors. Inflammatory markers, infection, homocysteine and sleep-disordered breathing rank as the four most important new risk factors in cerebral atherosclerosis. C-reactive protein is the inflammatory marker that has been most thoroughly studied. Elevated concentrations of C-reactive protein increase the risk of heart disease and thromboembolic stroke in men and women. The role of Chlamydia pneumoniae is still controversial. Influenza vaccination is a simple and effective preventive measure against stroke. Despite the potential relationship between homocysteine and stroke, we should wait to the results of the ongoing trials to know if the reduction of homocysteine levels with vitamin therapy is of clinical benefit. Sleep-disordered breathing is a potential new risk factor with an effective therapy. Neurologists should not forget to look for sleep disorders in their stroke patients and probably manage them with breathing therapy from the acute phase.
 ...
PMID:Cerebral ischemia: new risk factors. 1469 79

Over the past several decades, coronary artery disease (CAD) has become the major health problem in the Western world with more than 50% of deaths attributed to its complications. The exact causes of atherosclerosis are not clearly known, although multiple risk factors (e.g. hypertension, hyperlipidemia, diabetes mellitus, family history, and smoking) have been well described. However, these risk factors account for only about 50% of the total risk of CAD. Consequently, an ongoing search is under way to discover new risk factors for atherosclerosis as well as the basic underlying causes of progression. Although the evidence is not yet definitive, recent studies have shown that chronic infection by such bacterial organisms as Chlamydia pneumoniae, Helicobacter pylori, and a variety of dental pathogens may play a causative role in atherosclerosis. If this is true, then antimicrobial therapy may be helpful in the secondary prevention of CAD. Indeed, several small studies have already been completed testing this hypothesis. This article reviews the evidence associating these bacterial pathogens to CAD and presently available information regarding the use of antibiotics in the setting. At present, most studies evaluating the potential efficacy antimicrobials in the secondary prevention of CAD have tested the use of macrolide antibodies. Although several small preliminary studies have reported promising results favoring a clinical benefit from even short (<3 months) courses of antimicrobial therapy, the first large clinical trial, the Weekly Intervention with Zithromax for Atherosclerosis and its Related Disorders (WIZARD) study, did not show a statistically significant beneficial effect of a 3 month course of azithromycin over placebo by the end of up to 4 years follow-up. However, a statistically significant (p = 0.03) 33% reduction in death and myocardial infarction was found at 6 months, 3 months after the discontinuation of antibiotics. This robust clinical benefit, however, was not sustained over the ensuing 3.5 years of follow-up. These disappointing long-term outcomes of short-term therapy with antimicrobials may be explained by the recently discovered difficulty found in eradicating chronic vascular infections such as C. pneumoniae. It remains possible that longer term antimicrobial therapy or short-term use of more potent single agents or combinations, capable of effectively eradicating the offending organisms might provide added clinical benefit in the fight against CAD. Further studies are ongoing or planned to evaluate this potential. In the meantime, it is not presently recommended that antimicrobials be routinely prescribed for the secondary prevention of CAD.
 ...
PMID:Secondary prevention of coronary artery disease with antimicrobials: current status and future directions. 1472 86

By the turn of the last century, flying in the face of over a hundred years of research and clinical observation to the contrary, medicine abandoned the link between infection and atherogenesis; not because it was ever proven wrong, but because it did not fit in with the trends of a medical establishment convinced that chronic disease such as heart disease must be multifactorial, degenerative and non-infectious. Yet it was the very inability of 'established' risk factors such as hypercholesterolemia, hypertension and smoking to completely explain the incidence and trends in cardiovascular disease that resulted in historically repeated calls to search out an infectious cause, a search that began more than a century ago. Today, half of US heart attack victims have acceptable cholesterol levels and 25% or more have none of the "risk factors" associated with heart disease, including smoking, high blood pressure or obesity, most of which are not inconsistent with being caused by infection. Even the case of the traditionalist's latest 2003 JAMA assault to 'debunk' what they call the "50% risk factor myth" falls woefully short under scrutiny. In one group 30% died of heart disease with a cholesterol of at least 240 mg/dl, a condition which also existed in 21% who did not die during the same period. And the overlap was obvious throughout the so-called risk categories. Under such scrutiny, lead author Greenland conceded that if obesity, inactivity and elevated cholesteriol in the elderly are included, just about everyone has a risk factor and he likened the dilemma of people who do or do not wind up with heart disease akin to the susceptibility of people who are exposed to tuberculosis but do not get the disease. In Infections and Atherosclerosis: New Clues from an old Hypothesis? Nieto stressed the need to extend the possible role of infectious agents beyond the three infections which have in recent years been the focus of research: Cytomegalovirus (CMV) Chlamydia pneumoniae and Helicobactor pylori. Mycobacterial disease shares interesting connections to heart disease. Not only is tuberculosis the only microorganism to depend on cholesterol for its pathogenesis but CDC maps for cardiovascular disease bear a striking similarity to those of State and regional TB case rates. Ellis, Hektoen, Osler, McCallum, Swartz, Livingston and Alexander-Jackson all saw clinical and laboratory evidence of a causative relationship between the mycobacteria and heart disease. And Xu showed that proteins of mycobacterial origin actually led to experimental atherosclerosis in laboratory animals Furthermore present day markers suggested as indicators for heart disease susceptibility such as C-Reactive Protein (CRP), interleukin-6 and homocysteine are all similarly elevated in tuberculosis. It therefore behooves us to explore the link between heart disease and typical and atypical tuberculosis.
 ...
PMID:Heart disease: the greatest 'risk' factor of them all. 1508 5

Several parallels exist between preeclampsia and atherosclerosis. Both are multifactorial diseases that share risk factors such as obesity, insulin resistance, lipid abnormalities, and elevated serum homocysteine. There are also similarities in the biochemical changes seen in both diseases, including elevated serum triglycerides, decreased HDL cholesterol and enhanced formation of small, dense LDL particles as well as vascular atherosclerotic lesions. Chronic infection with Chlamydia pneumoniae has been linked to coronary artery disease. This study evaluated a possible link between the incidence of preeclampsia and infection with C. pneumoniae by examining the rate of seropositivity in 81 women with preeclampsia, and 206 women with normal pregnancies. Although our data confirmed well-known risk factors for preeclampsia such as obesity, diabetes, and hypertension, we found no difference in the rate of seropositivity between preeclampsia and normal pregnancy. On the contrary, the presence of chlamydial antibodies was lower in preeclampsia. Multiparous women with preeclampsia showed a significantly lower rate of seropositivity than multiparous normal women and nulliparous preeclamptics. In addition, women with a history of preeclampsia who developed preeclampsia in the current pregnancy also had a significantly lower rate of seropositivity.
 ...
PMID:Preeclampsia and Chlamydia pneumoniae: is there a link? 1536 46

Considerable progress has been made recently in understanding the pathobiology of atherosclerosis. To a significant degree it is an inflammatory disease of the vessel wall. Progression of atherosclerosis or its stabilization reflects the tension between cytokines and effectors that play both an inhibiting and a facilitating role in the progression of atherosclerosis, including platelet-derived growth factor (PDGF), interleukin-1, tumor necrosis factor (TNF) -alpha, and MCP-1. The response to injury model remains central to our understanding of atherogenesis. Numerous factors may initiate endothelial injury, including mechanical factors (hypertension and high shear stress in the artery), homocysteine, oxidized low-density lipoprotein (LDL), possibly infectious agents such as Chlamydia, viruses, and toxins such as nicotine. These factors lead to endothelial cells' increasing expression of receptors for LDL and increased adherence of monocytes and macrophages and T cells. Progression of atherosclerosis can lead to the development of a plaque that is vulnerable to rupture and that would then produce an acute coronary syndrome. In addition to standard biomarkers and angiographic approaches for detecting plaque rupture, novel diagnostic approaches are under development, including near infrared spectroscopy, catheter-based thermography, and optical coherence tomography. Our better understanding of the atherosclerotic plaque provides multiple opportunities for interdicting arterial injury, and the response to it.
 ...
PMID:Pathobiology of atherosclerosis--a brief review. 1563 Jun 73

To investigate the presence of infectious agents in human atherosclerotic arterial tissues. Atherosclerotic plaques were removed from 128 patients undergoing carotid endarterectomy or other bypass procedures for occlusive disease, and from twenty normal arterial wall samples, obtained from transplant donors with no history of diabetes, hypertension, smoking, or hyperlipidemia. Using the polymerase chain reaction (PCR) or reverse transcription-PCR, these samples were analyzed for the presence of Chlamydia pneumoniae, cytomegalovirus, enterovirus, adenovirus, herpes simplex viruses types 1 and 2, and Epstein-Barr virus. The amplicons were then sequenced, and phylogenetic analyses were performed. Enteroviral RNA was found in 22 of 128 atherosclerotic vascular lesions (17.2%), and C. pneumoniae and cytomegalovirus were each found in 2 samples (1.6%). In contrast, adenovirus, herpes simplex viruses, and Epstein-Barr virus were not identified in any of the atherosclerotic samples. Enterovirus was detected in 6/24 (25.0%) aortas, 7/33 (21.2%) carotid arteries, 6/40 (15.0%) femoral arteries, and 3/31 (9.7%) radial arteries of patients with chronic renal failure. There were no infectious agents detected in any of the control specimens. Using phylogenetic analysis, the enterovirus isolates were clustered into 3 groups, arranged as echovirus 9 and coxsackieviruses B1 and B3. Enteroviral RNA was detected in 17.2% of atherosclerotic plaques, but was not observed in any of the control specimens. This suggests a connection between enteroviral infection and atherosclerosis. These findings differ from those of other studies, which found more frequent incidence of C. pneumoniae and cytomegalovirus infection in atherosclerotic plaques.
 ...
PMID:Detection of enterovirus, cytomegalovirus, and Chlamydia pneumoniae in atheromas. 1565 Jun 86


<< Previous 1 2 3 4 5 6 7 Next >>