Animals ; Humans ; Ligands ; Polymorphism, Genetic ; Receptor Cross-Talk ; physiology ; Receptor, Angiotensin, Type 1 ; physiology ; Receptor, Angiotensin, Type 2 ; genetics ; physiology

OBJECTIVETo analyze the expression of angiotensin II (ANG II) receptor and apoptosis in myocardium in rats of endotoxemia.

METHODSModel of endotoxemia was induced by intraperitoneal injection with lipopolysaccharide (LPS) 10 mg/kg in male Wistar rats and saline was injected into control group. The rats were killed at 2 h or 6 h after saline (control) or LPS . Expression of the correlation factors related to apoptosis of Bcl-2, Bax, AT1 and AT2 receptor in myocardial tissue were detected with immunohistochemistry (IHC), and changes of myocardial cells apoptosis was detected by the method of TUNEL. The gene expression of AT1 and AT2 receptor was examined by RT-PCR. The pathological changes of myocardial tissue were observed by electron microscope.

RESULTSCompared with control group , the expression of AT1 and AT2 receptor were significantly decreased, especially in 6 h group; and the expression of Bcl-2 and Bax were decreased, the ratio of Bcl-2/Bax had the downtrend as well as the apoptosis of myocardial cells.

CONCLUSIONInterfered by LPS, the down regulation of AT1 and AT2 receptor expression has the negative relation with apoptosis of myocardial cells, this result indicated that down regulation of AT1 and AT2 receptor expression maybe related to cardiac functional impairment, which maybe help us to find a new protective path to prevent myocardial damage induced by systemic inflammatory.

Animals ; Apoptosis ; Endotoxemia ; metabolism ; Male ; Myocytes, Cardiac ; cytology ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar ; Receptor, Angiotensin, Type 1 ; metabolism ; Receptor, Angiotensin, Type 2 ; metabolism

To investigate the distribution frequencies of angiotensin-converting enzyme (ACE), angiotensinogen (AGT), angiotensin II I type receptor (AT1R) genotypes in Chinese, to find the relationships between polymorphisms of ACE, AGT and AT1R gene, and coronary artery thrombosis disease (CATD) and to study the interactions of themselves, PCR and PCR-RFLP techniques were performed to determine the genotypes of ACE, AGT and AT1R gene in CATD group (192 cases) and control group (110 cases). The results showed that (1) genotype frequencies of the three polymorphisms in the control group were 12.2% (DD), 43.9% (ID), and 43.9% (II) for the ACE I/D polymorphism; 8.2% (MM), 36.7% (MT), and 55.1% (TT) for AGT M235T polymorphism; 91.8% (AA), 8.2% (AC) for AT1R A1166C polymorphism respectively; (2) there were no significant differences between patients in either the control group, the non-MI group, or the MI group in any genotype frequency of all these three genes (P >0.05). (3) the odds ratio for CATD in subjects carrying both AT1R-AC and AGT-TT genotype was 3.517 (95% CI 0.988 - 12.527), compared with those carrying AT1R-AA and AGT-TT genotype and was 15.000 (95% CI 1.940-115.963), compared with those carrying AT1R-AC and AGT-MM/MT genotype. In subjects with AT1R-AC genotype, there was also a great difference of ACE D allele frequency between control group and CATD group (P=0.017). It is concluded that genotype frequencies of ACE I/D polymorphism, AGT M235T polymorphism, and AT1R A1166C polymorphism were obviously different from those in western countries. Although these three polymorphisms were not independent risk factors for CATD or myocardial infarction (MI) in Chinese, AT1R-AC genotype has a significant synergistic effect with AGT-TT genotype. There is also a obvious interaction between AT1R-AC genotype and ACE D allele.
Angiotensinogen ; genetics ; Coronary Thrombosis ; genetics ; Genotype ; Humans ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic ; Receptor, Angiotensin, Type 1 ; genetics

Essential hypertension is a multifactorial disease in which genetic and enviromental factors play an important role. These factors differ in each population. As there are no existing data for the Turkish population, we investigated four Renin Angiotensin System (RAS) gene polymorphisms, the angiotensin converting enzyme (ACE), angiotensinogen (AGN) M235T/T174M and angiotensin II type 1 receptor A1166C polymorphism in 109 hypertensive and 86 normotensive Turkish subjects. Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP), and agarose gel electrophoresis tecniques were used to determine these polymorphism. The frequencies of person that carry ACE D allel (DD+ID) was significantly higher in hypertensive group (99.1%) than controls (80%) (P<0.000). M235T TT genotype was also found significantly higher in hypertensives than control group (20% vs 2.7%; P<0.001). The frequency of AGN 174M allele was higher in the hypertensive group than control subjects (8.76% vs 4.81%). Frequency of ATR1 C allele (AC+CC genotypes) was found higher hypertensives than controls (39.4% vs 25.9%; P = 0.054). Our results suggest that an interaction exists between the RAS genes and hypertension in Turkish population.
Angiotensinogen/*genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertension/*genetics ; Male ; Middle Aged ; Peptidyl-Dipeptidase A/*genetics ; Polymorphism, Genetic/*genetics ; Receptor, Angiotensin, Type 1/*genetics ; Renin-Angiotensin System ; Turkey

Hepatitis B, Chronic ; metabolism ; Humans ; Liver Cirrhosis ; metabolism ; RNA, Messenger ; analysis ; Receptor, Angiotensin, Type 1 ; genetics ; Renin ; genetics

OBJECTIVETo identify the A1166/C polymorphism of angiotensin II type 1 receptor (AT1R) gene in patients with essential hypertension complicated with brain infarction (BI).

METHODSAT1R genotyping with polymerase chain reaction-restrictive fragment length polymorphism was performed in 70 normotensive subjects, 72 hypertensive patients without cardio-cerebrovascular diseases(EH-NCCVD) and 70 hypertensive patients with BI. The relationship between the polymorphism of AT1R gene and plasma lipid levels was also studied.

RESULTSThe frequencies of C allele in the two groups of hypertension were higher than that in the health controls, respectively (P<0.05). But there was no significant difference in the frequency of C allele between the two groups of hypertension. A positive correlation was observed between the lipoprotein(a) and AT1R gene A1166/C polymorphism in hypertensive patients.

CONCLUSIONAT1R gene contributes to the development of essential hypertensive, but not to the incidence of BI in the hypertensive.

Aged ; Alleles ; Brain Infarction ; complications ; Female ; Gene Frequency ; Humans ; Hypertension ; blood ; complications ; genetics ; Lipids ; blood ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptor, Angiotensin, Type 1 ; Receptors, Angiotensin ; genetics

Antisense Elements (Genetics) ; Cell Line ; Cell Proliferation ; Collagen Type I ; biosynthesis ; Genetic Therapy ; Hepatic Stellate Cells ; cytology ; metabolism ; Humans ; RNA, Messenger ; genetics ; Receptor, Angiotensin, Type 1 ; genetics ; Transfection

OBJECTIVETo characterize if irbesartan regulates vascular inflammatory gene expression profiles related to atherosclerosis in EA.hy926 cells.

METHODSHuman umbilical vein endothelial cell line EA.hy926 cultured in vitro was incubated with irbesartan (1×10(-6) mol/L) for 24 h. The total RNA was extracted from the cells for gene expression profiling. The DAVID Gene Functional Classification Tool was used to analyze the disease- and function-related genes in the cells. Real-time quantitative polymerase chain reaction (RT-PCR) was used to verify the genes showing differential expression after irbesartan treatment. The protein levels of angiotensin II type 1 receptor (AT1R) and type 2 receptor (AT2R) were tested by Western blotting.

RESULTSCompared with the control cells, 56 genes were found to show marked changes following irbesartan treatment, including 39 up-regulated and 17 down-regulated genes. Disease analysis suggested that these genes were related to such diseases as coronary atherosclerosis, myocardial infarction, and colorectal cancer. Eight genes, namely MMP2, PTGS2, PECAM1, SELP, SELL, CYP1A1, MMRN1, and HSPA1A, were involved in atherosclerosis and myocardial infarction. Verification by RT-PCR produced a result consistent with the gene array result. AT1R was down-regulated while AT2R up-regulated in irbesartan-treated cells.

CONCLUSIONIrbesartan regulates the inflammatory gene expressions related to atherosclerosis in EA.hy926 cells. These inflammatory factors may promote destabilization of atherosclerotic plaque possibly in relation to AT2R overexpression.

Angiotensin II Type 1 Receptor Blockers ; pharmacology ; Atherosclerosis ; genetics ; pathology ; prevention & control ; Biphenyl Compounds ; pharmacology ; Cell Line ; Cytoprotection ; Gene Expression Profiling ; Human Umbilical Vein Endothelial Cells ; drug effects ; pathology ; Humans ; Inflammation ; genetics ; Receptor, Angiotensin, Type 1 ; genetics ; Receptor, Angiotensin, Type 2 ; genetics ; Tetrazoles ; pharmacology

BACKGROUNDMany studies have suggested that angiotensin II (Ang II) and its receptors may be involved in the development of asthma. However, the expression of angiotensin II receptors (AGTR) is not clear in the lung tissue of chronic asthmatics. This study was designed to determine the relationship between airway remodeling, dysfunction and the expression of AGTRs in a rat model of asthma.

METHODSRats were sensitized with ovalbumin (OVA) for 2 weeks. Sixty minutes before an inhalation challenge, the rats were pretreated either with valsartan (15, 30, 50 mg x kg(-1) x d(-1)) or saline intragastrically. Then the rats received an OVA challenge for 30 alternative days. Acetylcholine (Ach)-induced bronchoconstriction was measured after the final antigen challenge. White cell counts in bronchoalveolar lavage fluid (BALF) and morphological changes in the airways were then assessed. The levels of transforming growth factor-beta 1 (TGF-beta(1)) and platelet-derived growth factor (PDGF) in BALF were detected by ELISA. The levels of AGTR1 and AGTR2 mRNA and protein in lung tissues were measured by RT-PCR and Western blotting.

RESULTSAGTR1 mRNA and protein levels in repeatedly OVA-challenged rats were significantly increased as compared with negative controls. The AGTR1 mRNA expression versus white cell counts of BALF and airway wall thickness (mainly in small airways) in lungs of chronic antigen-exposed rats were positively correlated. Valsartan decreased the level of AGTR1 in repeatedly OVA-challenged rats. However, AGTR2 mRNA and protein levels in the OVA-challenged rats and high-dose valsartan-treated rats (50 mg x kg(-1) x d(-1)) were also increased. Valsartan significantly decreased inflammatory cell accumulation and attenuated Ach-evoked bronchoconstriction in repeatedly antigen-challenged rats. Valsartan also decreased allergen-induced structural changes in rat airway (including total airway wall thickness and smooth muscle area) and the levels of TGF-beta(1) and PDGF in BALF.

CONCLUSIONSAGTR1 expression is potentially associated with airway remodeling and dysfunction in asthma. Ang II and AGTR1 may participate in airway inflammation and airway remodeling of chronic antigen-exposed rats. Valsartan, a AGTR1 antagonist, could inhibit AGTR1 expression and partially inhibits structural airway changes as well as airway inflammation in chronic OVA-exposed rats.

Angiotensin II Type 1 Receptor Blockers ; pharmacology ; Angiotensin Receptor Antagonists ; Animals ; Asthma ; chemically induced ; genetics ; metabolism ; Blotting, Western ; Bronchoalveolar Lavage Fluid ; chemistry ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; drug effects ; Lung ; drug effects ; metabolism ; pathology ; Male ; Ovalbumin ; Platelet-Derived Growth Factor ; metabolism ; Rats ; Rats, Wistar ; Receptor, Angiotensin, Type 1 ; genetics ; metabolism ; Receptor, Angiotensin, Type 2 ; genetics ; metabolism ; Receptors, Angiotensin ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tetrazoles ; pharmacology ; Transforming Growth Factor beta1 ; metabolism ; Valine ; analogs & derivatives ; pharmacology ; Valsartan

To explore the relation of angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) gene polymorphism with coronary heart disease (CHD) and the severity of coronary artery stenosis, 130 CHD patients who underwent coronary angiography were examined for the number of affected coronary vessels (> or = 75% stenosis) and coronary Jeopardy score. The insertion/deletion of ACE gene polymorphism and AT1R gene polymorphism (an A-->C transversion at nucleotide position 1166) were detected by using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) in CHD patients and 90 healthy serving as controls. The results showed that DD genotype and of ACE were more frequent in CHD patients than that in control group (38.5% vs 14.4%, P<0.001). The frequency of the AT1R A/C genotypes did not differ between the patients and the controls (10% vs 13.1%, P>0.05). The relative risk associated with the ACE-DD was increased by AT1R-AC genotype. Neither the number of affected coronary vessels nor the coronary score differed among the ACE I/D genotypes (P>0.05). But the number of affected coronary vessels and the coronary score were significantly greater in the patients with the AT1R-AC genotype than in those with the AA genotype (P<0.05). In conclusion, DD genotype may be risk factor for CHD and MI in Chinese people, and is not responsible for the development of the coronary artery stenosis. The AT1R-C allele may increase the relative risk associated with the ACE-DD genotype, and may be involved in the development of the stenosis of coronary artery.
Coronary Disease/genetics ; Coronary Disease/pathology ; Coronary Stenosis/*genetics ; Coronary Stenosis/*pathology ; Peptidyl-Dipeptidase A/*genetics ; Polymorphism, Genetic ; Receptor, Angiotensin, Type 1/*genetics