Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the past decade, several novel risk factors for atherosclerosis, including inflammation and infections, have been reported. Seroepidemiological studies suggest an association between several microbes and coronary heart disease. Microbes or their structural components are found in atherosclerotic plaques, but the only intact microbes commonly present are herpes viruses and Chlamydia pneumoniae. These agents are able to initiate and accelerate atherosclerosis in animal models. If they cause persistent infection in the vessel wall, they can directly promote a proinflammatory, procoagulant, and proatherogenic environment. Microbes could also have a remote effect--e.g., bacterial heat shock proteins with high sequence homology with human counterpart could, in the presence of a chronic infection, induce autoimmunity against vascular cells, and lead to an atherosclerotic process. Several intervention trials with antibiotics are underway, and will hopefully shed new light on the role of bacteria in atherosclerosis. The causal relationship can be proved by use of vaccination to prevent infections.
 ...
PMID:Evidence for infectious agents in cardiovascular disease and atherosclerosis. 1189 89

Whether or not infectious agents are involved in the pathogenesis of atherosclerosis has been a matter of discussion for the past 2 decades. Although there is no definite proof of a causal role of human cytomegalovirus in atherogenesis, a body of knowledge supports the concept that this virus is involved in the development of atherosclerotic lesions. This review assesses the most important data published in support of this hypothesis.
Herpes 2002 Apr
PMID:Opinion article: cytomegalovirus is a risk factor in atherogenesis. 1191 96

Over the last few years emerging evidence indicate the involvement of herpes viruses in the pathogenesis of several medical complications in transplanted patients. Herpes viruses are transmitted via inter-human contact and cause a primary infection, which commonly fails to give clinical signs and may persist even for years in a latent state in healthy subjects. In transplanted patients, herpes viruses may be transmitted through the transplanted organ or may be reactivated because of the use of powerful immunosuppressive drugs. Moreover, the persistence of immunosuppression greatly favours the clinical expression and severity of virus infection. Thus, herpes viruses seem to be involved in both acute and chronic deterioration of graft function, in the pathogenesis of post-transplant lymphoproliferative disorders and Kaposi sarcoma, and even in vessel atherosclerosis. This review will focus on relevant clinical aspects of herpes-virus infection, namely cytomegalovirus, EBV, herpes simplex 1 and 2, varicella zoster virus, HHV-6, HHV-7 and HHV-8, in kidney transplanted patients.
 ...
PMID:[Herpetic viruses and renal transplantation]. 1219

The article describes the clinical, virological and immunological data confirming the etiological role of herpes virus in the initiation of atherosclerosis. 226 patients with atherosclerosis of the predominantly coronary localization were examined; hypertension and stenocardia were found in a part of them, while myocardial infarction was diagnosed in 22% of the patients. The control group consisted of patients with other diseases related with infections (bronchial asthma, rheumatism etc.) as well as of healthy persons. A total of 558 patients were examined and it was established that there is a reliable relation between atherosclerosis and the infection of patients with, mainly, herpes virus. The correlation was of the seasonal nature, it was linked to the specific features of an infection process and it was confirmed by the condition of the cholesterol supply and by immunodeficiency in patients. The infectious nature of atherosclerosis demands further research for the sake of finding proof of the etiological role of viruses and bacteria and for the sake of working out the means of prophylaxis and treatment of atherosclerosis aimed at removing the infectious etiological factor.
 ...
PMID:[Role of viral-herpetic infections in the etiology of atherosclerosis: clinical, virological and immunological evidence]. 1274 52

Various herpes- and poxviruses contain DNA sequences encoding proteins with homology to cellular chemokine receptors, which belong to the family of G protein-coupled receptors (GPCRs). Since GPCRs play a crucial role in cellular communication and chemokine receptors play a prominent role in the immune system, the virally encoded GPCRs may be crucial determinants of viral action. The Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus 8), implicated in the pathogenesis of Kaposi's sarcoma (KS), a highly vascularized tumor, encodes a GPCR, referred to as ORF74. This virally encoded receptor was found to induce tumorigenesis and transgenic expression of ORF74 induces an angioproliferative disease resembling KS. Cytomegalovirus (CMV), suggested to play a role in atherosclerosis, encodes four GPCRs, among which US28. This virally encoded GPCR is able to induce migration of smooth muscle cells, a feature essential for the development of atherosclerosis. Remarkably, the KSHV and some CMV-encoded GPCRs display constitutive activity, while their cellular homologs do not. It remains to be determined whether this phenomenon contributes to the pathogenesis of viral action. Also, the family of poxviruses encodes GPCRs of which the function is not clear yet. In this review we will give an overview of the different virally encoded GPCRs, and discuss their putative role in viral action and potential as drug target.
 ...
PMID:Virally encoded G protein-coupled receptors: targets for potentially innovative anti-viral drug development. 1281 50

On a variety of fronts, chronic infection has been found to be significantly associated with the development of atherosclerosis and the clinical complications of unstable angina, myocardial infarction, and stroke. For the most part, these relationships are still just associations. Failure to confirm initial reports of serologic associations also has been common. Specific causative relationships on par with that determined between H pylori and peptic ulcer disease have not yet been established. Potential mechanisms whereby chronic infections may play a role in atherogenesis are myriad. In the case of C pneumoniae, the effect may result from direct vessel wall colonization that may damage the vessel either directly or indirectly by initiating immunologic responses. In other cases the effect may simply be that of enhancing the pre-existing chronic inflammatory response of the body to standard risk factors such as hyperlipidemia. Even though the infectious agent may not directly infect the vessel wall, it may perform its critical role from afar. Chronic infection might also influence pre-existing plaque by enhancing T-cell activation or other inflammatory responses that may participate in the destabilization of the intimal cap. Hence chronic infection may play a role either in the initiation, progression, or the destabilization of atherosclerotic plaques. The infectious agents with the most evidence to support an etiologic role in atherosclerosis include C pneumoniae and cytomegalovirus. Evidence is mounting for a variety of other potential agents including other herpes viruses, influenza, other specific bacteria (such as M pneumoniae), and chronic infections with common bacterial agents (periodontal disease, chronic bronchitis, and chronic urinary tract infection, among others) [191]. Future studies are expected to elucidate further the pathophysiologic relationship between chronic infection and atherosclerosis and to evaluate further the potential of a variety of treatment approaches, including antibiotics.
 ...
PMID:Chronic infection and coronary artery disease. 1462 50

Although the metabolic syndrome together with insulin resistance and their consequences are probably basic factors in pathogenesis of atherosclerosis, inflammatory and infectious aspects of this process are unquestionable only in some of the patients. Endothelial dysfunction was identified both in the experiment and in patients after herpes virus simplex 1 infection, cytomegaloviral infection, Chlamydia pneumoniae infection, or Helicobacter pylori infection. However, it is not clear whether it is always caused by direct specific activity of a given pathogen or whether it is a result of inflammatory cytokines activity, heat shock protein activity, or CRP activity. In recent years secondary antibiotic prevention in patients after myocardial infarction has been discussed. Lower mortality rate from acute myocardial infarction and cerebral vascular accidents were found in several observations of patients vaccinated against influenza. In patients with non-stable angina pectoris we have found significantly more frequent occurrence of IgG antibodies against Chlamydia pneumoniae. This occurrence was more frequent in diabetics compared to non-diabetics. Endothelia exposed to cyto-megaloviral infection exprimed adhesive molecules on their surfaces. After an increase of the concentration of glucose in medium to 11.0 mmol/l and 16.5 mmol/l the expression of adhesive molecules after cyto-megaloviral infection increased. Relationship of infection, inflammation, and atherosclerosis has been a subject of intensive investigation in recent years. Discussion of possible consequences of these findings, especially from viewpoint of atherosclerosis prevention and its organ complications, is of the same intensity. Hypothesis about participation of infection and inflammation in pathogenesis of atherosclerosis seems to be very attractive. In spite of the fact that findings supporting this hypothesis cumulate final conclusion can't be made yet.
 ...
PMID:[Infectious and inflammatory factors in the etiology and pathogenesis of atherosclerosis]. 1504 Jan 64

Atherosclerosis is the leading cause of death in the United States, and human cytomegalovirus (HCMV), a member of the herpes virus family, may play a role in the development of the disease. We previously showed that HCMV regulated endothelial apoptosis. In this study, we investigated the induction of apoptosis and signal transduction pathways regulating this process in HCMV-infected endothelial cells. As observed previously, HCMV induced a typical cytopathic effect in human aortic endothelial cells (HAECs), ie, the formation of single nucleated or multinucleated giant cells. Although infected HAECs were resistant to apoptosis at earlier stages of infection, they became apoptotic with prolonged infection as demonstrated by positive staining using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). This apoptotic process was mediated by the caspase-dependent mitochondrial apoptotic pathway as indicated by increased expression and cleavage of caspases 3 and 9 as well as increased expressions of pro-apoptotic molecules Bax and Bak. Blocking caspases 3 or 9 significantly inhibited the HCMV-induced apoptosis. Further exploration of the upstream pathway demonstrated upregulation of the tumor suppressor p53 gene and activation of the ataxia telangiectasia mutant (ATM) pathway in the infected cells. Blocking p53 inhibited HCMV-stimulated Bax and Bak expression as well as caspase-3 activation and blocking the ATM pathway inhibited HCMV-stimulated p53 activation. Although early infection may render cells antiapoptotic, prolonged infection, however, induced endothelial apoptosis through ATM and p53-dependent activation of the mitochondrial death pathway. This proapoptotic effect may be relevant to endothelial dysfunction and HCMV-associated vascular diseases.
 ...
PMID:Human cytomegalovirus causes endothelial injury through the ataxia telangiectasia mutant and p53 DNA damage signaling pathways. 1510 95

The discovery of the physico-chemical host defence is closely connected with the endotoxin research. It is well known that the toxic effects of endotoxins under experimental conditions can be induced only when they are administered parenterally. However, in naturally occurring entero-endotoxemic diseases (e.g. septic and various shocks, etc.), the endotoxin is absorbed from the intestinal tract. The cause and mode of translocation have been unknown. The generally used experimental shock models differ from natural diseases only in the mode by which endotoxin enters the blood circulation. If the common bile duct of rats was chronically canulated (bile-deprived animals) orally administered endotoxin was absorbed from the intestinal tract into blood circulation and provoked endotoxin shock. This translocation of endotoxins and the consequent shock can be prevented by sodium deoxycholate or natural biles. The bile acids split the endotoxin macromolecule into atoxic fragments. A similar detoxifying detergent action plays a significant role in host defence against infectious agents with outer lipoprotein structure (e.g. so-called 'big' viruses). This defence mechanism of macroorganisms based on the detergent activity of bile acids (end-products of the cholesterol metabolism) is called as physico-chemical defence system. Therefore, bile deficiency and the consequent endotoxemia are important components in the pathogenesis of certain diseases (e.g. sepsis, intestinal syndrome of radiation disease, hepato-renal syndrome, parvovirus infection, herpes, psoriasis, atherosclerosis, etc.). Bile acids may be used for the prevention and/or therapy of the above mentioned clinical conditions.
 ...
PMID:Bile acids in physico-chemical host defence. 1556 10

Chronic inflammatory stimulus seems to contribute to atherosclerotic process. Several studies have established a relationship between infective agents as Chlamydia pneumoniae, herpes virus and cytomegalovirus and atherosclerotic lesions. Aim of this study was to investigate the effects of influenza infective state on endothelial function of healthy young subjects, expressed as brachial flow-mediated vasodilation (FMV) and soluble form of intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1). In 10 male subjects (mean age 35+/-14 years) exhibiting influenza symptoms for 3 days, we determined total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, sVCAM-1, sICAM-1 and brachial FMV. All subjects had an antibody pattern characteristic of influenza A or B virus infection. After 3 months brachial FMV was significantly increased (8.6+/-2.3% versus 11.5+/-3.2%; p<0.001), while HDL (46+/-10 mg/dL versus 49+/-9 mg/dL; p<0.05), sICAM-1 and sVCAM-1 were reduced (respectively: 488+/-105 ng/mL versus 340+/-127 ng/mL; p<0.001, 1710+/-80 ng/mL versus 1216+/-63 ng/mL; p<0.001). Univariate analysis showed a positive correlation between changes in CRP and sICAM-1 levels (r=0.95, p<0.001), a negative one between changes in sICAM-1 and brachial FMV (r=-0.65, p<0.05) and between CRP and brachial FMV (r=-0.64, p<0.05). This small study suggested that inflammatory state determined by viral agents may transitorily alter endothelial function in healthy subjects.
Atherosclerosis 2005 Feb
PMID:Acute inflammatory state during influenza infection and endothelial function. 1569 44


<< Previous 1 2 3 4 5 Next >>