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)

Hyperfibrinogenemia is a common feature of the nephrotic syndrome, and contributes to increased tendency for thrombosis and atherosclerosis. Its genesis is not certain, but the increase in liver fibrinogen mRNA in nephrotic rats indicates increased synthesis. Data in humans are scarce. We presently compared synthesis rates of fibrinogen and albumin in nephrotic adults (N = 7; plasma albumin 22.3 +/- 0.7 g/liter, proteinuria 12 g/day) and healthy control subjects (N = 8) using a primed/continuous infusion of the stable isotope L-[1-13C]valine for six hours. Absolute synthesis rate (ASR) of fibrinogen was 31 +/- 3 mg/kg/day in nephrotic subjects and 21 +/- 1 mg/kg/day in control subjects (P < 0.05), and positively correlated with plasma fibrinogen (P = 0.0317). The plasma fibrinogen pool was disproportionately increased in the nephrotic patients (271 +/- 30 mg/kg) compared to the controls (126 +/- 8 mg/kg), suggesting decreased fractional catabolic rate as well. The ASR of albumin was increased from 71 +/- 4 mg/kg/day in the controls to 160 +/- 19 mg/kg/day in the patients (P < 0.0001), and strongly correlated with the ASR of fibrinogen (P = 0.0046). Plasma alpha 2-macroglobulin was also elevated and correlated with the albumin synthesis rate, whereas plasma serum amyloid A and C-reactive protein were not elevated. These data suggest that in nephrotic patients the increased albumin synthesis is associated with an increase in synthesis of a specific and coordinated group of proteins, among which is fibrinogen.
 ...
PMID:Proportionate increase of fibrinogen and albumin synthesis in nephrotic patients: measurements with stable isotopes. 945 16

An increasing body of evidence has linked infections to atherosclerosis and thrombosis. Herpesviruses cause atherosclerosis in experimental animals. Herpesviruses can also be detected in atherosclerotic lesions in humans. Cytomegalovirus may play a role in arteriosclerosis in transplanted hearts, and this virus, together with tumor suppressor protein p53, can be found in restenosis lesions following angioplasty. Chlamydia pneumoniae and dental infections are associated with coronary heart disease in cross-sectional and longitudinal studies, and preceding respiratory infections are associated with ischemic stroke. Infections may favor formation of atherosclerosis and thrombosis by elevation of blood levels of fibrinogen, leukocytes, clotting factor, and cytokines and by alteration of the metabolism and functions of endothelial cells and monocyte macrophages. Low-grade infections may also be one of the causes of the inflammatory reaction observed in atherosclerotic lesions and acute ischemic symptoms, reflected in elevated levels of C-reactive protein. These observations warrant further studies in this field.
 ...
PMID:Role of infection as a risk factor for atherosclerosis, myocardial infarction, and stroke. 952 51

Atherosclerosis is characterized as a chronic inflammatory-fibroproliferative disease of the vessel wall. The attachment of monocytes and T-lymphocytes to the injured endothelium followed by their migration into the intima is one of the first and most crucial steps in lesion development. The co-localization of CD4+ T-cells and macrophages in the lesion, the abundant expression of HLA Class II molecules and the co-stimulatory molecule CD40 and its ligand (CD40L) indicate a contribution of cell-mediated immunity to atherogenesis. Transgenic mouse models revealed that dependent on the model T- and B-cells may promote lesion progression, monocytes and macrophages are in contrast essential for the development of atherosclerotic lesions. Apart from the local process in the vessel wall, systemic signs of an inflammatory reaction are also associated with lesion development. Thus plasma levels of C-reactive protein and fibrinogen and the white blood cell count are positively correlated to the risk of cardiovascular disease. Recently, an inflammatory phenotype of circulating peripheral blood monocytes could be demonstrated as a specific cellular correlate to lipid and lipoprotein risk factors. Thus the pool size of LPS receptor (CD14)dim and Fc gamma IIIa receptor (CD16a)+ monocytes positively correlates to plasma cholesterol levels, to triglycerides levels and to the apolipoprotein E4 (apo E4) phenotype in contrast to a negative correlation to the high density lipoprotein (HDL) cholesterol concentration. This CD14dim CD16a+ monocytes are further characterized by a high expression of beta 1- and beta 2-integrins, suggesting a higher capacity for attachment at sites of inflammation. A proinflammatory cytokine pattern and an expansion of these cells in other inflammatory diseases are indicating that these cells promote the inflammatory process during atherogenesis. Surface expression of the activation antigen CD45RA on monocytes in correlation to plasma LDL cholesterol and Lp(a) levels further indicates an inflammatory reaction. Regarding the potential mechanisms of the phenotypic changes of peripheral blood monocytes, in a serum free in vitro differentiation model supplemented with M-CSF monocytes from probands which are homozygous for apo E4 showed a significantly higher increase of CD16a expression compared to apo E3/E3 cells indicating that a genetic polymorphism of a single apolipoprotein gene locus may affect monocyte differentiation. The further characterization of the cellular immunology of monocytes and T-lymphocytes in lesion development will provide new specific diagnostic and therapeutic targets in atherogenesis.
 ...
PMID:T-lymphocytes and monocytes in atherogenesis. 964 98

In the last years several new data allow a controversial but convincing interpretation of the pathogenesis of atherosclerosis (arteriosclerosis). Atherosclerosis can be apparently the result of ultrachronic persistent infection by Chlamydia pneumoniae and not the result of different risk factors. The main arguments for the chlamydial genesis are: 1. Correlation of coronary heart disease and other atherosclerotic disease with antibodies against C. pneumoniae. 2. C. pneumoniae could be detected with different techniques (PCR, immunohistology, electromicroscopy, culture) in a high percentage in atheromas from different sites. 3. Three international studies with macrolides in coronary heart disease were successful. 4. The target cells of atherosclerosis (endothelia, macrophages, muscle cells) can be infected by C. pneumoniae in vitro. 5. Positive animal experiments. The Koch-Henle criteria for the proof of the etiology are largely fulfilled--even if there are doubts about the validity of these criteria in chronic local infections. A number of unexplainable aspect of atherosclerosis can be seen in a new light. The higher incidence of coronary heart disease in young males has a parallel in the remarkable androtropism of many bacterial diseases (pneumococcal pneumonia, tuberculosis). The reduction of incidence of atherosclerotic diseases since 1965 can be explained by the much higher intake of doxycyclin and macrolides. The low incidence of coronary heart disease in France--sometimes regarded as an effect of red wine--can be explained as a result of a much higher use of antichlamydial antibiotics. The increase of inflammatory parameters (C-reactive protein, fibrinogen, leucocytes) before acute coronary infarction are not risk factors but signs of an active chronic infection. The interpretation is possible, that atherogenic changes in lipids like increase of LDL and decrease of HDL are not risk factors but consequence of chronic arterial infection by chlamydia. The low incidence of atherosclerosis in the tropics--despite high frequency of chlamydial infection--is difficult to explain. Vascular infection can be related with the age of the patient at the primary infection. With low hygiene, intestinal primary infections in early childhood can be possible. Arterial infection would be thus a result of a primary infection in adolescence ("yet another poliomyelitis story"). There are good arguments for the thesis that C. pneumoniae is the primary cause of atherosclerosis and not a secondary invader. The consequence, nevertheless, is similar: Antibiotics get a key role. The macrolides roxithromycin, azithromycin, clarithromycin and the tetracyclin doxycyclin fulfill the criteria as potential antichlamydial agents. In general a longer treatment (6 to 8 to 12 weeks) seems advisable. It is necessary to start international studies with antibiotics in coronary infarction and other clinical manifestations of atherosclerosis. The relevant antibiotics licensed for chlamydial infections are cheap and safe. Despite of the urgent need for controlled studies, it seems already justified to treat high-risk patients with antibiotics. Meticulous protocols and long-term control of patients are necessary to evaluate the therapeutic effects. Preventive studies in patients without clinical manifestation of atherosclerosis are urgently needed. The risks of resistance or side effects are neglectable, but the organisation of such studies would be very difficult.
 ...
PMID:[Arteriosclerosis as a sequela of chronic Chlamydia pneumoniae infection]. 964

Peroxisome proliferator-activated receptors (PPARs) are key players in lipid and glucose metabolism and are implicated in metabolic disorders predisposing to atherosclerosis, such as dyslipidaemia and diabetes. Whereas PPARgamma promotes lipid storage by regulating adipocyte differentiation, PPARalpha stimulates the beta-oxidative degradation of fatty acids. PPARalpha-deficient mice show a prolonged response to inflammatory stimuli, suggesting that PPARalpha is also a modulator of inflammation. Hypolipidaemic fibrate drugs are PPARalpha ligands that inhibit the progressive formation of atherosclerotic lesions, which involves chronic inflammatory processes, even in the absence of their atherogenic lipoprotein-lowering effect. Here we show that PPARalpha is expressed in human aortic smooth-muscle cells, which participate in plaque formation and post-angioplasty re-stenosis. In these smooth-muscle cells, we find that PPARalpha ligands, and not PPARgamma ligands, inhibit interleukin-1-induced production of interleukin-6 and prostaglandin and expression of cyclooxygenase-2. This inhibition of cyclooxygenase-2 induction occurs transcriptionally as a result of PPARalpha repression of NF-kappaB signalling. In hyperlipidaemic patients, fenofibrate treatment decreases the plasma concentrations of interleukin-6, fibrinogen and C-reactive protein. We conclude that activators of PPARalpha inhibit the inflammatory response of aortic smooth-muscle cells and decrease the concentration of plasma acute-phase proteins, indicating that PPARalpha in the vascular wall may influence the process of atherosclerosis and re-stenosis.
 ...
PMID:Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not by PPARgamma activators. 965 93

Serum lipoproteins including lipoprotein(a), Lp(a), are emerging as possible biological markers for cerebrovascular disease. Existing data on Lp(a) and serum lipids levels following acute ischemic stroke (AIS) are however equivocal. To determine whether serum Lp(a) and other lipid levels obtained within 24 h of acute ischemic stroke onset changed over the ensuing 4 weeks and whether these levels are related to an acute phase response, acquired nutritional deficiency, and neurovascular data, we conducted repeated measurement analyses among 19 subjects (mean age 65.0 +/- 12.1 years; 32% women) presenting with AIS (evaluated within 9.7 +/- 12.7 h). Eleven of the subjects had a moderate-to-severe stroke, defined by NIH stroke severity scale, and seven patients had a large cerebral infarction. Seven serial measurements of Lp(a), total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and other lipoproteins, major acute phase reactants and albumin levels were collected for each subject over 4 weeks. The mean initial levels, (mg/dl), of total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, Lp(a), apolipoproteins A-I and B were: 225 +/- 57.6, 154 +/- 56.0, 40 +/- 10.4, 181 +/- 93.7, 52 +/- 28.6, 130 +/- 24.6, and 141 +/- 46.1, respectively. There were no significant changes in mean serum lipid, apolipoprotein or Lp(a) levels over the 4-week study period, analyzed by a random effects model to test for time trend. In addition, there were no significant changes in established acute phase or nutritional markers (C-reactive protein, alpha 1-glycoprotein, haptoglobin or serum albumin). Our findings suggest that serum lipid, apolipoprotein and Lp(a) levels remain stable following AIS, consistent with the absence of acute phase response or nutritional deficiency.
Atherosclerosis 1998 Aug
PMID:Lipid and lipoprotein levels remain stable in acute ischemic stroke: the Northern Manhattan Stroke Study. 971 47

Type II (non-insulin-dependent) diabetes mellitus is associated with increased blood concentrations of markers of the acute-phase response, including sialic acid, alpha-1 acid glycoprotein, serum amyloid A, C-reactive protein and cortisol, and the main cytokine mediator of the response, interleukin-6. The dyslipidaemia common in Type II diabetes (hypertriglyceridaemia and low serum levels of HDL cholesterol) is also a feature of natural and experimental acute-phase reactions. We review evidence that a long-term cytokine-mediated acute-phase reaction occurs in Type II diabetes and is part of a wide-ranging innate immune response. Through the action of cytokines on the brain, liver, endothelium, adipose tissue and elsewhere, this process could be a major contributor to the biochemical and clinical features of metabolic syndrome X (glucose intolerance, dyslipidaemia, insulin resistance, hypertension, central obesity, accelerated atherosclerosis) but also provides a mechanism for many other abnormalities seen in Type II diabetes, including those in blood clotting, the reproductive system, metal ion metabolism, psychological behaviour and capillary permeability. In the short-term, the innate immune system restores homeostasis after environmental threats; we suggest that in Type II diabetes and impaired glucose tolerance long-term lifestyle and environmental stimulants, probably in those with an innately hypersensitive acute-phase response, produce disease instead of repair.
 ...
PMID:Is type II diabetes mellitus a disease of the innate immune system? 1023 Jun 57

Disruption of atherosclerotic plaques with associated thrombus is responsible for the majority of the acute coronary syndromes. Plaque instability is related closely to the degree of inflammation. Inflammatory cells within the plaque produce cytokines that inhibit collagen production by vascular smooth muscle cells and increase the production of metalloproteinases, which degrade the extracellular matrix in the fibrous cap. The recruitment of inflammatory cells into the vessel wall occurs in a coordinated sequence of events involving the expression of cellular adhesion molecules on the surface of activated endothelial cells and the production of chemoattractants, and occurs in part in response to oxidation of low-density lipoprotein within the vessel wall. The cellular adhesion molecules are shed into the circulating blood in several disease states, including clinically evident atherosclerosis. The acute-phase reactants C-reactive protein and interleukin-6, and markers of the fibrinolytic state (plasminogen activator inhibitor-1 and tissue plasminogen activator), are also elevated in the acute coronary syndromes and in healthy individuals at increased risk for developing coronary artery disease. These markers may reflect vascular inflammation and thereby the stability of atherosclerotic plaques. Their measurement may pinpoint the mechanisms of benefit of cholesterol-lowering therapy and other interventions designed to reduce coronary risk, and potentially could offer a new method for monitoring coronary risk factor reduction in patients.
 ...
PMID:Inflammation, the endothelium, and the acute coronary syndromes. 988 50

A number of newer, "nontraditional" cardiovascular risk factors have been identified based on recent studies of the pathogenesis of atherosclerosis and atherothrombotic cardiovascular events. These include chronic inflammation and its markers, such as C-reactive protein; homocysteine; oxidative stress or endothelial dysfunction; lipoprotein Lp (a); psychosocial factors, such as environmental stress and responsiveness to stress; plasma insulin levels and markers of insulin resistance; and activation of the renin-angiotensin system, which is in part a function of polymorphisms in genes for components of the system, such as angiotensinogen and the angiotensin II type 1 receptor. The strength of the associations of the newer risk factors with cardiovascular therapy are currently being tested. This review will briefly discuss evidence that these risk factors are related to cardiovascular disease.
 ...
PMID:Nontraditional cardiovascular risk factors. 1010 Jun 94

Fragments of apolipoprotein(a) [apo(a)], the distinctive glycoprotein of lipoprotein(a) [Lp(a)], are present in human plasma and urine and have been implicated in the development of atherosclerosis. The mechanism responsible for the generation of apo(a) fragments in vivo is poorly understood. In this study, we examined the plasma levels of Lp(a) and apo(a) fragments [or free apo(a)] and urinary apo(a) in 15 subjects who underwent cardiac surgery necessitating cardiopulmonary bypass. We also measured the plasma concentration and activity of polymorphonuclear elastase, an Lp(a)-cleaving enzyme in vitro, and plasma levels of C-reactive protein. Despite a marked activation of polymorphonuclear cells and a pronounced inflammatory response, as documented by an 8-fold and a 35-fold increase in plasma levels of polymorphonuclear elastase and C-reactive protein, respectively, the proportion of plasma free apo(a) to Lp(a) and urinary excretion of apo(a) remained unchanged over a 7-day period after surgery, and polymorphonuclear elastase activity remained undetectable in plasma. No fragmentation of apo(a) was observed ex vivo in plasma samples collected before and after surgery. These data indicate that in this model, apo(a) is not fragmented in plasma and are consistent with the hypothesis that apo(a) fragments result from a constitutively active tissue mechanism that is not modified by cardiac surgery with cardiopulmonary bypass.
 ...
PMID:Effect of cardiopulmonary bypass and heparin on plasma levels of Lp(a) and Apo(a) fragments. 1019 36


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>