Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic glomerulosclerosis is defined by increased glomerular extracellular matrix (ECM) that is mainly synthesized by mesangial cells that underwent an activation mediated by cytokines and growth factors from various cellular origins. In this study, we tested whether macrophages could infiltrate the glomeruli and influence ECM synthesis in experimental diabetes. To test our hypothesis, we initially studied the dynamics of glomerular macrophage recruitment in streptozotocin-induced diabetic rats at days 1, 2, 4, 8, 15, and 30 by using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) on isolated glomeruli and immunohistochemistry and morphometry. We then assessed the role of macrophages on the basis of the pharmacological modulation of their recruitment by insulin or ACE inhibitor treatments and by X-irradiation-induced macrophage depletion at days 8 and 30. Macrophages were recruited within the glomeruli at the very early phase of hyperglycemia by using RT-PCR CD14 detection from day 2 and by using ED1 immunohistochemistry from day 8. This glomerular macrophage infiltration was associated with an increase in alpha1-chain type IV collagen mRNA. In parallel, the diabetic glomeruli became hypertrophic with an increase in the mesangial area. Macrophage recruitment was preceded by or associated with an increased glomerular expression of vascular cell adhesion molecule 1, intracellular adhesion molecule 1, and monocyte chemoattractant protein 1, which contributes to monocyte diapedesis. Glomerular interleukin-1beta mRNA synthesis was also enhanced as early as day 1 and could be involved in the increase in ECM and adhesion molecule gene expressions. Insulin treatment and irradiation-induced macrophage depletion completely prevented the glomerular macrophage recruitment and decreased alpha1-chain type IV collagen mRNA and mesangial area in diabetic rats, whereas ACE inhibitor treatment had an incomplete effect. It can be concluded that in the streptozotocin model, hyperglycemia is followed by an early macrophage recruitment that contributes to the molecular and structural events that could lead to glomerulosclerosis. Therefore, besides direct stimulation of mesangial cells by hyperglycemia, macrophages recruited in the glomeruli during the early phase of hyperglycemia could secondarily act on mesangial cells.
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PMID:Early glomerular macrophage recruitment in streptozotocin-induced diabetic rats. 1086 70

Vascular access thrombosis (VAT) remains a significant problem worldwide. This study determined the association between VAT and 7 candidate gene polymorphisms (factor V Leiden 1691G>A, factor II 20210G>A, methylenetetrahydrofolate reductase 677C>T, angiotensin converting enzyme 287 base pair (bp) insertion/deletion, transforming growth factor-beta1 869T>C and 915G>C, NOS3 -786T>C and intron 4 27 bp tandem repeat, and endotoxin receptor CD14 -159C>T). This was a retrospective case-control pilot study conducted in 101 hemodialysis patients at a large tertiary-care, University health-science center. Sixty cases that experienced frequent VAT and 41 controls that had not experienced VAT in at least 3 years were evaluated for demographics and genotyping. These data were summarized, and univariable and multivariable regression models were constructed. Univariate VAT predictors included the NOS3 420 bp allele (P=0.03) and the presence of a central venous dialysis catheter (P<0.01). Aspirin use was protective against VAT (P=0.02). In the multivariate analysis, the dialysis access type remained a significant predictor of thrombosis (P<0.01), while aspirin use retained its protective status (P=0.01). Statin use was associated with the cases (P=0.02); however, the NOS3 420 bp allele failed to improve the model. These data confirm that central venous dialysis catheter access is associated with thrombosis, while aspirin use appears protective. The NOS3 420 bp allele may have an association with thrombosis; however, further epidemiologic data evaluating large dialysis registries are needed to confirm our observation.
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PMID:A pilot study of genetic polymorphisms and hemodialysis vascular access thrombosis. 1921 Feb 73

BACKGROUND: Current drug therapy of atherosclerosis is focused on treatment of major risk factors, e.g. hypercholesterolemia while in the future direct disease modification might provide additional benefits. However, development of medicines targeting vascular wall disease is complicated by the lack of reliable biomarkers. In this study, we took a novel approach to identify circulating biomarkers indicative of drug efficacy by reducing the complexity of the in vivo system to the level where neither disease progression nor drug treatment was associated with the changes in plasma cholesterol. RESULTS: ApoE-/- mice were treated with an ACE inhibitor ramipril and HMG-CoA reductase inhibitor simvastatin. Ramipril significantly reduced the size of atherosclerotic plaques in brachiocephalic arteries, however simvastatin paradoxically stimulated atherogenesis. Both effects occurred without changes in plasma cholesterol. Blood and vascular samples were obtained from the same animals. In the whole blood RNA samples, expression of MMP9, CD14 and IL-1RN reflected pro-and anti-atherogenic drug effects. In the plasma, several proteins, e.g. IL-1beta, IL-18 and MMP9 followed similar trends while protein readout was less sensitive than RNA analysis. CONCLUSION: In this study, we have identified inflammation-related whole blood RNA and plasma protein markers reflecting anti-atherogenic effects of ramipril and pro-atherogenic effects of simwastatin in a mouse model of atherosclerosis. This opens an opportunity for early, non-invasive detection of direct drug effects on atherosclerotic plaques in complex in vivo systems.
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PMID:Circulating Markers Reflect Both Anti- and Pro-Atherogenic Drug Effects in ApoE-Deficient Mice. 1957 2

Our aim was to define the distribution of monocyte subsets in a cohort of congestive heart failure (CHF) patients, to verify whether increased severity of CHF is linked to the expansion of specific monocyte subsets, and finally to investigate the relationship between monocyte subset relative frequencies, laboratory parameters of inflammation, and monocyte ACE expression. Thirty consecutive CHF patients and 26 healthy control subjects were evaluated for peripheral blood monocyte expression of CD14, CD16 and CD143 (ACE) by flow-cytometry, and for endothelial-derived soluble CD146 levels by ELISA. CD14++ CD16+ frequency was significantly higher in CHF patients than in Controls (%, median value and IQ) (12.3, 8.7-14.8 vs 5.9, 4.7-6.9, p< 0.05, CHF vs Controls), and it increased depending on how high NYHA class was, on worsening LV ejection fraction and on circulating pro-BNP values. Furthermore, it was associated with increasing creatinine and with decreasing GFR and albumin levels. Monocyte CD143 expression was significantly elevated in CHF patients as compared to Controls, and positively associated with CD14++ CD16+ levels. Frequencies of CD14+ CD16+ monocytes were significantly lower in CHF patients as compared to Controls, and negatively correlated with levels of soluble CD146 (r=-0.529; p 0.048). In conclusion, monocytic CD14++ CD16+ frequency and CD143 levels are increased and reflect disease status and progressive cardiac deterioration in CHF patients. The CD14+ CD16+ subset is depleted in CHF and is linked to endothelial damage in this group of patients. Although the question of whether differences in monocyte CD14CD16 expansion are causal or whether they represent a marker of HF progression which is potentially relevant for risk prediction remains unanswered, we believe that our data represent an important tool for exploring the role of selective inflammatory pathways in CHF progression.
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PMID:CD14CD16 monocyte subset levels in heart failure patients. 2036 47

Renin-angiotensin system, metabolic abnormalities, and immune activity have a role in the pathogenesis of primary hypertension. We assessed the leukocyte mRNA expression of angiotensinogen, angiotensin converting enzyme, renin, angiotensin 2 type 1 receptor, CD14 molecule, adiponectin type 1 receptor, and leptin receptor in hypertensive children before and after nonpharmacological treatment. Leukocyte mRNA expression was measured by means of quantitative real-time reverse transcriptase-polymerase chain reaction in 23 hypertensive children before and after 6 months of nonpharmacological treatment based on dietary advice and physical activities. Twenty-three normotensive children matched for age, sex, and body mass index served as a control group. Before treatment patients had elevated expression of angiotensin converting enzyme and CD14 mRNA, decreased expression of angiotensinogen and angiotensin type 1 receptor mRNA, and unchanged expression of renin, adiponectin, and leptin receptors mRNA as compared with controls. Renin mRNA negatively correlated with 24-hour mean arterial pressure and carotid intima-media thickness. Six months of nonpharmacological treatment caused decrease of blood pressure and normalization of metabolic abnormalities. Renin, adiponectin, and leptin receptors mRNA expression decreased and were lower than in control group. Changes in blood pressure, left ventricular mass, carotid intima-media thickness, body mass index, and waist circumference did not correlate with changes in the expression of renin-angiotensin system genes, CD14, leptin, and adiponectin receptors mRNA. We conclude that leukocytes of hypertensive children displayed alterations in the expression of renin-angiotensin system genes as well as those of CD14. Nonpharmacological treatment resulted in downregulation of genes involved in renin-angiotensin activation and those engaged in leukocyte responses to adipokines.
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PMID:Altered genes profile of renin-angiotensin system, immune system, and adipokines receptors in leukocytes of children with primary hypertension. 2326 43