Efficacy and tolerability of a single-pill combination of telmisartan/hydrochlorothiazide 80/25 mg in Chinese and Korean patients with moderate to severe hypertension: a subgroup analysis of a randomized, double-blind, active-controlled trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hypertension is an important issue in Asia, responsible for up to 66% of cardiovascular disease cases. This randomized controlled trial subgroup analysis compared telmisartan 80 mg (T80)/hydrochlorothiazide 25 mg (H25) singlepill combination with T80 monotherapy, specifically in Chinese and Korean patients.</p><p><b>METHODS</b>Patients with grade 2/3 hypertension were randomized to receive telmisartan 40 mg (T40)/hydrochlorothiazide 12.5 mg (H12.5) combination or T40 monotherapy for one week, before uptitrating the dose to T80/H25 or T80, respectively, for the remaining 6 weeks. The primary endpoint was systolic blood pressure (SBP) mean change from baseline. Secondary endpoints included mean diastolic blood pressure (DBP) change from baseline, and blood pressure (BP) goal achievement. Adverse events were recorded.</p><p><b>RESULTS</b>Of a total 888 patients who were treated, efficacy analyses for Chinese and Korean patients included 127 patients treated with T80/H25 and 54 patients treated with T80. At week 7, mean SBP reductions from baseline were -37.5 mmHg (1 mmHg = 0.133 kPa) and -26.9 mmHg in the T80/H25 and T80 groups (adjusted mean difference, -10.6 mmHg; 95% confidence interval (CI), -15.6 to -5.7). Mean DBP reductions were -19.0 and -14.1 mmHg in the T80/H25 and T80 groups (adjusted mean difference, -4.9 mmHg; 95% CI, -8.0 to -1.8). In total, 56.7% of patients receiving T80/H25 achieved BP goal (<140/90 mmHg) compared with 35.2% receiving T80. SBP goal attainment (<140 mmHg) and DBP goal attainment (<90 mmHg) were also higher in the T80/H25 group compared with the T80 group (SBP: 69.3% vs. 48.1%; DBP: 62.2% vs. 46.3%). A small number of treatment-related adverse events were observed in both T80/H25 (nine patients, 6.9%) and T80 monotherapy (two patients, 3.6%) groups.</p><p><b>CONCLUSIONS</b>In Chinese and Korean patients with moderate-to-severe hypertension, treatment with T80/H25 provided large reductions in mean SBP and DBP, and high BP goal attainment rates. This once-daily combination is effective and well tolerated in this patient group.</p>

Effects of amlodipine plus telmisartan or amlodipine plus amiloride regimen on blood pressure control in hypertensive patients: preliminary report of Chinese Hypertension Intervention Efficacy (CHIEF) trial / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the effects of amlodipine-based antihypertensive combination regimen on blood pressure control and impact on cardiovascular events.</p><p><b>METHODS</b>From Oct. 2007 to Oct. 2008, a total of 13 542 hypertensive patients from 180 centers in China were included in this multi-centre randomized, controlled, blind-endpoint assessment clinical trial. Inclusion criteria were: essential hypertension, 50 - 79 years of age with at least one cardiovascular risk factor and signed consent forms. Patients were randomly assigned to receive low-dose amlodipine + diuretics (group A) or low-dose amlodipine + telmisartan (group T). The primary endpoints are composite of non-fatal stroke/myocardial infarction and cardiovascular death. All patients will be followed-up for 4 years.</p><p><b>RESULTS</b>The characteristics of patients between the two groups were similar: mean age (61.5 +/- 7.7) Yrs with 19% history of cerebrovascular diseases, 12% coronary diseases, 18% diabetes, 42% dyslipidemia, mean initial blood pressure 157/93 mm Hg. After 8-week treatment, mean blood pressure in group A and B were reduced to (133.0 +/- 11.0)/(81.0 +/- 7.6) mm Hg, (132.9 +/- 11.6)/(80.6 +/- 7.9) mm Hg respectively. Blood pressure control rates reached 72.1% and 72.6% in group A and T, respectively.</p><p><b>CONCLUSION</b>Amlodipine-based antihypertensive combination regimens achieved satisfactory blood pressure control rate in patients with essential hypertension in this patient cohort.</p>

A randomized, double-blind, double-dummy study comparing a fixed dose combination of telmisartan 80 mg plus hydrochlorothiazide 12.5 mg to telmisartan 80 mg in Chinese hypertensive patients who failed to respond adequately to telmisartan 80 mg / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of a fixed dose combination of telmisartan 80 mg plus hydrochlorothiazide (HCTZ) 12.5 mg (TH) to telmisartan 80 mg (T) in Chinese patients who failed to respond adequately to treatment with T.</p><p><b>METHOD</b>This is a multi-center, randomized, double-blind, double-dummy clinical study. A total of 699 eligible hypertensive patients entered a one-week screening phase prior to the eight-week open-label T period. At the end of eight weeks, 345 patients who failed to respond to T (DBP > or = 90 mm Hg, 1 mm Hg = 0.133 kPa) were randomized to receive either TH (175 patients) or T (170 patients) for another eight weeks. Sitting and standing BP were taken 24 hours post-dose and adverse events were documented at visit with 4 weeks interval. Laboratory, ECG and physical examination were performed at screening, at baseline and at the final visit.</p><p><b>RESULTS</b>After 8 weeks treatment, (1) The mean trough reduction in sitting diastolic blood pressure (SiDBP) from baseline in TH group was greater than that in T group (10.1 mm Hg vs 7.7 mm Hg, P = 0.0017). The mean trough reduction in sitting systolic blood pressure (SiSBP) from baseline was 14.2 mm Hg in TH group and 7.4 mm Hg in T group (P < 0.0001). (2) The mean trough reduction in standing DBP and standing SBP from baseline were significantly greater in TH group (8.7 mm Hg and 12.9 mm Hg) compared those in T group (7.3 mm Hg and 7.0 mmHg, P = 0.0350, P < 0.0001). (3) The number and percentage of responders in TH group (129, 74.6%) were significantly higher than in T group (100, 59.2%, P = 0.0016). (4) The incidence of the study drug-related adverse events was similar between TH and T group (3.5% vs. 3.6%, P > 0.05).</p><p><b>CONCLUSION</b>TH was more effective than T in patients not responded adequately to T in Chinese hypertensive patients.</p>

Incidence of metabolic disorders in patients with essential hypertension and patients with primary aldosteronism / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the incidence of metabolic disorders (MS) in patients with primary aldosteronism (PA) and essential hypertension (EH).</p><p><b>METHODS</b>MS prevalence was observed in 200 EH patients (male 104) and 220 PA patients (male 117) hospitalized to our hospital from August 2005 to March 2007.</p><p><b>RESULTS</b>(1) The prevalence of MS in PA group was significantly higher than that of EH group (47.3% vs. 31.5%, P = 0.009). (2) Blood pressure was significantly higher in PA group than that of EH [SBP: (150.67 +/- 15.45) mm Hg vs. (145.69 +/- 17.13) mm Hg, P = 0.042; DBP: (93.03 +/- 10.51) mm Hg vs. (85.83 +/- 14.44) mm Hg, P = 0.037]. (3) Incidences of abdominal obesity (86.8% vs. 78.5%, P = 0.024) and insulin resistance (insulin sensitivity index: 42.42 +/- 16.11 vs. 49.58 +/- 22.43, P = 0.008) were significantly higher in PA group than in EH group.</p><p><b>CONCLUSION</b>The prevalence of MS in hospitalized PA patients was significantly higher than that of EH patients characterized by prevalent abdominal obesity, insulin resistant and severe hypertension.</p>

Differential expression of microRNAs in the aorta of spontaneously hypertensive rats / 生理学报

MicroRNAs (miRNAs) are genomically encoded non-protein-encoding small RNAs, which negatively regulate target gene expression at post-transcriptional level. The present study aimed to investigate whether disorders of miRNAs system were involved in the pathogenesis of hypertension in spontaneously hypertensive rats (SHR). MiRanda, Target Scan and PicTar were utilized for predictive analysis of miRNAs and target genes. MiR-1, miR-133a, miR-155 and miR-208 were selected as the candidate miRNAs potentially related to blood pressure. The expression levels of miR-1, miR-133a, miR-155 and miR-208 in the aorta of 4-, 8-, 16- and 24-week-old SHR and age-matched Wistar-Kyoto (WKY) rats were detected by real-time RT-PCR. The mRNA levels of angiotensin II receptor type 1 (AGTR1a), angiotensin II receptor associated protein (AGTRAP), divalent metal transporter 1 (DMT1), low-density lipoprotein-related protein 1B (LRP1B), fibroblast growth factor-7 (FGF-7), protocadherin 9 precursor (PCDH9), chloride channel protein 5 (CLCN-5), small conductance calcium activated potassium channel protein 3 (KCNN3) and thyroid hormone receptor associated protein 1 (THRAP1), which were predicted to be target genes of differentially expressed miRNAs, were further detected by real-time RT-PCR. The results obtained showed that the expression levels of miR-1, miR-155 and miR-208 in the aorta were significantly different from those in the heart of WKY rats. The miR-155 level was significantly lower in aorta of 16-week-old SHR than that of age-matched WKY rats (P<0.05), but there was no difference between SHR and WKY rats in other age groups. In addition, miR-155 level was negatively correlated to blood pressure (r=-0.525, P<0.05). Both in WKY rats and SHR, miR-208 was most abundantly expressed in 4-week-old rats, but declined significantly in 8-, 16- and 24-week-old rats (P<0.05). No difference in miR-208 levels was observed between age-matched SHR and WKY rats. Moreover, miR-208 expression in aorta was negatively correlated with blood pressure (r=-0.400, P<0.05) and age (r=-0.684, P<0.0001). Neither miR-1 nor miR-133a was differentially expressed in SHR and WKY rats in different age groups. The mRNA levels of predicted target genes were not correlated to miR-155 or miR-208 levels. These results indicate that miR-155 is less expressed in the aorta of adult SHR compared with that of WKY rats and is negatively correlated with blood pressure, suggesting it is possibly involved in the development and pathologic progress of hypertension. The miR-208 expression in rat aorta declines with aging and it may play a role in the blood vessel development.

Kynurenine Aminotransferase and Kynurenic Acid in Spontaneous Hypertensive Rats / 中华高血压杂志

0.05).The concentration of urinary KYNA,metabolite of the KYN,was significantly lower in SHRs compared to WKYs(7.8?1.8 vs 19.9?3.5 ?mol/24 h P=0.013).Both KAT activity in renal cortex and KYNA content in urine were negatively correlated to blood pressure(r=-0.418,P=0.023;r=-0.723,P=0.001).Conclusion The declined activity of KAT in renal cortex and the deficiency of KYNA concentration in urinary may affect blood pressure regulation in SHR by renal metabolite of the KYN.

Association between uroguanylin G-247A polymorphism and blood pressure/fluid and electrolytes homeostasis / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the association between uroguanylin G-247A polymorphism and blood pressure/fluid and electrolytes homeostasis.</p><p><b>METHODS</b>Uroguanylin genotype was determined by restrictive fragment length polymorphism (RFLP) and blood pressure as well as fluid and electrolytes homeostasis were measured in 442 volunteers from Jing Ning County, ZheJiang Province. Data were analyzed by ANOVA, Generalized Estimating Equations (GEE), and Quantitative Transmission Disequilibrium Test (QTDT).</p><p><b>RESULTS</b>Ten uroguanylin gene polymorphisms were detected in 40 subjects by direct sequencing, all were reported in the NCBI SNP database. We selected the G-247A polymorphism for genotyping. Compared with G allele carriers, AA homozygotes had a higher urinary volume (P = 0.08), higher excretions of sodium (P = 0.07) and potassium (P < 0.001), but similar systolic and diastolic blood pressure (P > 0.32) both before and after adjustment for sex, age, body-mass index, current smoking, alcohol intake, and antihypertensive treatment.</p><p><b>CONCLUSIONS</b>The uroguanylin G-247A polymorphism was associated with urinary volume and sodium and potassium excretions.</p>

Study on insulin resistance and genetic polymorphisms in essential hypertension patients of two different kinds of TCM constitution / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the relationship of insulin resistance and the polymorphisms of insulin receptor-related genes in essential hypertension patients of two different kinds of TCM constitution.</p><p><b>METHODS</b>Oral glucose tolerance test (OGTT) and insulin release test (InRT) were conducted in 217 essential hypertensive patients of either sluggish meticulous (SM) constitution (139 cases) or prosperous impetuous (PI) constitution (78 cases), and the polymorphism of three genes, including insulin-like growth factor-1 receptor (IGF-1R), insulin receptor substrate-1 (IRS-1) and 2 (IRS-2) genes were detected.</p><p><b>RESULTS</b>(1) OGTT, InRT and insulin resistance index (Homa-IR) were higher and insulin sensitive index (ISI) was lower in the patients of SM constitution than those in patients of PI constitution. (2) Significant difference of ISI and Homa-IR was shown in patients of both constitutions with genotype G of the 3 genes.</p><p><b>CONCLUSION</b>Decrease of insulin sensitivity and increase of insulin resistance are more obvious in hypertensive patients with genotype G of the 3 genes of SM constitution than in those of PI constitution. Therefore, the difference in constitution might be one of the genetic characteristics for insulin resistance in hypertensive patients.</p>

Prevalence and risk factors of asymptomatic intracranial vascular stenosis in patients with essential hypertension / 中华心血管病杂志

<p><b>OBJECTIVE</b>The aim of the study was to determine the prevalence and the distribution pattern of lesion site of intracranial vascular stenosis and to identify risk factors for the stenosis in patients with essential hypertension.</p><p><b>METHODS</b>A total of 231 consecutive inpatients with essential hypertension were included in this study. Patients with the history of cerebrovascular diseases and relevant neurological symptoms were excluded. Intracranial vascular stenosis (>50% diameter reduction) was detected using CT angiography (CTA).</p><p><b>RESULTS</b>Of 231 patients, 69 (29.87%) had intracranial artery stenosis. The most common stenosis site is middle cerebral artery (43.69%), followed by carotid siphon (20.39%). The stenosis in internal carotid arterial system (78.64%) was more common than in vertebrobasilar arterial system (21.56%, P < 0.05). The patients with intracranial vascular stenosis were older, had longer history of hypertension, higher levels of systolic blood pressure, higher plasma cholesterol, higher LDL-C. Lp (a), higher urinary microalbumin excretion, thicker ventricular septum, and lower levels of HDL-C than the patients without stenosis. Logistic analysis showed that systolic blood pressure (OR 1.650, 95% CI 1.134 - 2.400, P = 0.023), course of hypertension (OR 1.238, 95% CI 1.072 - 1.429, P = 0.006), LDL-C (OR 2.103, 95% CI 1.157 - 3.823, P = 0.014) and type 2 diabetes (OR 2.325, 95% CI 1.161 - 4.341, P = 0.011) were the independent risk factors of asymptomatic intracranial arterial stenosis.</p><p><b>CONCLUSIONS</b>Nearly 30% inpatients with essential hypertension had asymptomatic intracranial artery stenosis. The most common site of stenosis was middle cerebral artery. Hypertension, dyslipidemia and diabetes were risk factors for the development of intracranial arterial stenosis.</p>

Determination of Activity of Human Lymphocyte Kynureninase / 上海第二医科大学学报

Objective To develop an efficient method for the determination of activity of human lymphocyte kynureninase by high performance liquid chromatography. Methods Protein containing kynureninase was extracted from lymphocytes.The reaction was made with 3-hydroxyanthranilic acid as substrate and pyridoxal-5'-phosphate as coenzyme.The product was determined by high performance liquid chromatography and fluorescence detection.(Results)Standard curve of 3-hydroxyanthranilic acid was highly linear over the range from 2 to 400 nmol/L.The intra-day coefficient of variation(CV) was less than 3.0% and the inter-day CV was less than 3.2%. Conclusion(The developed) assay is efficient and can be used to determine the activity of kynureninase from kinds of tissues.

Mutation screening of RET proto-oncogene in Chinese sporadic patients with pheochromocytoma / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To screen the mutations of RET proto-oncogene in sporadic patients with pheochromocytoma.</p><p><b>METHODS</b>Forty-two cases of sporadic pheochromocytoma were tested for mutations of RET gene. Of these 42 DNA samples, 12 were extracted from peripheral blood cells and 30 from paraffin-embedded pheochromocytoma specimens. The PCR product of exon 10 and exon 11 was used to molecular analysis of the RET proto-oncogene.</p><p><b>RESULTS</b>Among 42 patients, 2 were found to have RET gene mutations. One of mutations located at codon 634 (TGC>TAC) in exon 11 of RET proto-oncogene. Another one located at codon 632 (GAG>AAG).</p><p><b>CONCLUSION</b>Some patients with apparently sporadic pheochromacytoma were carrier of mutations, a routine genetic analysis for mutations of RET gene is indicated for these patients.</p>

Gene profile for differentiation of vascular adventitial myofibroblasts / 生理学报

Our previous study demonstrated that TGF-beta1 could induce the differentiation of vascular adventitial fibroblasts (AFs) to myofibroblasts (MFs). The aim of this study was to identify the genes which might be responsible for the cell phenotypic change using genechips. Cultured rat AFs were treated with TGF-beta1 (10 ng/ml) for 0 min, 5 min, 15 min, 2 h, 12 h and 24 h, respectively. Then the cells were gathered to prepare total RNA. We examined TGF-beta1-induced gene expression profiling using Affymetrix oligonucleotide microarrays and analyzed data by GCOS1.2 software. Moreover, expressional similarity was measured by hierarchical clustering. Some of genechip results were confirmed by real-time quantitative RT-PCR. Microarray analysis identified 2121 genes with a 2-fold change or above after TGF-beta1 stimulation. 1318 genes showed a greater than 2-fold increase and 761 genes were reduced 2 folds or more at mRNA levels, whereas a small portion of the total regulated genes (42 genes) displayed dynamically up- and down-regulated pattern. Genes were further segregated for early (peak at 5 min, 15 min and/or 2 h), late (peak at 12 h and/or 24 h), and sustained (2-fold change or above at five time points) temporal response groups according to the time of their peak expression level. Among 1318 up-regulated genes, 333 genes (25.3%) responded rapidly to TGF-beta1 and 159 genes (12.1%) responded in a sustained manner. Most genes (826, 62.6%) were regulated at 12 h or later. For the 761 down-regulated genes, numbers of early and late responsive genes were 335 (44%) and 267 (36.1%), respectively. There were also 159 genes, 19.9% of total down-regulated genes, decreased at five time points treated by TGF-beta1. The results suggested that the gene expressions of secreted phosphoprotein 1 (APP1) and Rho-associated coiled-coil forming kinase 2 (ROCK2) had the same trends as alpha-smooth muscle-actin, a marker of MF differentiation. In addition, the gene expression of potassium voltage-gated channel, Shal-related family and member 2 (KCND2) was up-regulated. Furthermore, it was found that endothelin 1 (EDN1), some complement components, NADPH oxidase 4 (NOX4) and NAD(P)H dehydrogenase, quinone 1 (NQO1) might be involved in MF differentiation. Using microarrary technique, we confirmed some genes that have been identified by other techniques were implicated in MF differentiation and observed new genes involved in this process. Our results suggest that gene expression profiling study is helpful in identifying genes and pathways potentially involved in cell differentiation.

Aldosterone-to-renin ratio threshold for screening primary aldosteronism in Chinese hypertensive patients / 中华心血管病杂志

<p><b>OBJECTIVE</b>In recent years, the assessment of the plasma aldosterone-to-renin ratio (ARR) has become a most effectively and commonly used method for screening primary aldosteronism from hypertensive patients. It is known that there is a large variance in ARR value between races and ARR is affected by many factors, such as drugs, posture and serum potassium etc. The objective of this study is to establish the threshold of ARR for screening primary aldosteronism in Chinese hypertensive patients.</p><p><b>METHODS</b>A total of 110 hypertensive patients were recruited and divided into essential hypertension group (n=65) and adenoma/hyperplasia group (n=45) according to the adrenal contrast CT scan. Antihypertensive drugs which can affect ARR such as beta-blockers, dihydropyridine calcium channel blockers (CCBs), ACE inhibitors (ACEIs), angiotensin II receptor blockers (ARBs) and clonidine, were withdrawn for at least 2 weeks. Washout period for diuretics including spironolactone were 4 weeks. Non-dihydropyridine calcium channel blockers (slow released verapamil) and/or alpha-blocker (terazosin) are allowed for controlling blood pressure when needed. If the serum potassium value<3.6 mmol/L, an oral potassium supplement was prescribed. After keeping upright position for 2 hours, blood samples were drawn for PRA and PAC measurement between 9:00AM-10:00AM.</p><p><b>RESULTS</b>ARR was 100.00+/-48.65 (14.19-285.16) pg/ml vs ngxml-1xh-1 in patients with essential hypertension and 699.33+/-213.33 (185.8-2150) pg/ml vs ngxml-1xh-1 in patients with adenoma/hyperplasia. ARR value was greater than 240 in 42 out of 45 patients (93.3%) with adenoma/hyperplasia and was less than 240 in 59 out of 65 (90.7%) patients with essential hypertension. We used ARR 240 as the cut-off threshold for screening primary aldosteronism in another 178 hypertensive patients and ARR was greater than 240 in all 15 patients with confirmed primary aldosteronism.</p><p><b>CONCLUSION</b>It is suitable to use upright ARR 240 as a cut-off threshold for screening primary aldosteronism in Chinese hypertensive patients.</p>

Efficacy and safety of olmesartan medoxomil versus losartan potassium in Chinese patients with mild to moderate essential hypertension / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of olmesartan medoxomil compared with losartan potassium in patients with mild to moderate essential hypertension.</p><p><b>METHOD</b>This is a randomized, double-blind, double-dummy, active-controlled, parallel, multi-center study. After a 2-week placebo run-in period, a total of 287 eligible subjects were randomized at 1:1 ratio to receive olmesartan medoxomil 20 mg or losartan potassium 50 mg, once daily for 8 weeks. The blood pressure was assessed after 4 weeks treatment. If the subject's seating diastolic blood pressure (SeDBP) was still >or=90 mm Hg, the dosage was doubled for another 4 weeks; for those subjects whose SeDBP was <90 mm Hg after 4-week treatment, the initial dosage remained unchanged and the treatment continued until completion of the study.</p><p><b>RESULTS</b>(1) The mean trough reduction in SeDBP from baseline in olmesartan group was significantly greater than that in losartan group after 4 weeks (11.72 mm Hg vs 9.23 mm Hg, P=0.004) and 8 weeks treatment (12.94 mm Hg vs 11.01 mm Hg, P=0.035). (2) The number and percentage of responders in olmesartan group (81, 65.3%) were statistically higher than those (68, 52.7%) in losartan group (P=0.028) after 4 weeks treatment and were similar between the two groups after 8 weeks treatment (P>0.05). (3) Individual and overall trough/peak ratios of DBP and SBP in 24-hour ambulatory blood pressure monitoring were higher in olmesartan group than losartan group. The hypotensive effect of olmesartan was more durable than losartan at 24 hour interval. (4) The incidence of study drug-related adverse events (AEs) in olmesartan group (10.5%) was similar as that in losartan group (13.9%, P>0.05). Most of these AEs were mild and transient.</p><p><b>CONCLUSION</b>This study shows that olmesartan medoxomil, at oral dose of 20 mg-40 mg once daily was effective and safe for hypertension treatment and the hypotensive effect was superior to losartan potassium (50 mg-100 mg once daily).</p>

No association between 3 polymorphisms of transforming growth factor beta3 gene and essential hypertension in Chinese / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate possible association between the single nucleotide polymorphisms (SNPs) of transforming growth factor beta3 (TGF-beta3) gene and essential hypertension (EH) in Chinese.</p><p><b>METHODS</b>The promoter region, exons, as well as part of the introns of TGF-beta3 gene were sequenced by a fluorescent labeling automatic sequencing method to detect and characterize the SNPs in 24 DNA samples from a Chinese population. Then we conducted a case-control study using 396 patients with hypertension (case) and 214 nomortensive subjects (control). The three SNPs including Thr63Asn, SS5608219 and SS5608220 were genotyped by PCR-RFLP or real-time allele-specific PCR in subjects studied.</p><p><b>RESULTS</b>Seven SNPs in the exons, introns and 3'untranslated region (3'UTR) of TGF-beta3 gene were identified. Among them, 2 SNPs were found to be novel genetic variants and one of the two located in the exon 1 and produced substitution of amino acid. However, no differences were found between hypertensives and nomortensives in genotype distribution and allele frequency of SS5608219, Thr63Asn or SS5608220 polymorphisms.</p><p><b>CONCLUSIONS</b>Two novel SNPs of TGF-beta3 gene were identified in Chinese. One of them produces a threonine to asparagines substitution in codon 63 (Thr63Asn). But no association was found between TGF-beta3 gene polymorphisms and EH in Chinese.</p>

Number of circulating endothelial progenitor cells inversely correlate with the severity of coronary artery disease in patients with stable coronary artery disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate whether the number of circulating endothelial progenitor cells (EPCs) correlate with the severity of coronary stenosis in patients with stable coronary artery disease (CAD).</p><p><b>METHODS</b>80 consecutive patients who underwent coronary angiography (exclusion of acute coronary syndrome and myocardial infarction) were enrolled. Physical examination and blood tests were performed to assess the disease severity and cardiovascular risk factors. Circulating EPCs as measured by the number of CD133/KDR double positive cells were detected by FACS.</p><p><b>RESULTS</b>The number of EPCs inversely correlated with age, creatinine clearance (Ccr) and left ventricular mass index (LVMI) (P = 0.004, 0.015, 0.014 respectively). Patients with hypertension showed significant reduction in number of EPCs compared to those without hypertension (P = 0.004). Moreover, the number of EPCs in patients with coronary artery disease was significantly lower than that of those with normal coronary artery (P < 0.01). EPCs also inversely correlated with angiographic Gensini score (n = 49, r = -0.305, P = 0.039).</p><p><b>CONCLUSIONS</b>In patients with stable CAD, the numbers of circulating EPCs correlate with the severity of CAD as well as cardiovascular risk factors.</p>

P38 MAPK was involved in angiotensin-induced migratory potential of adventitial fibroblasts from spontaneously hypertensive rat / 中华心血管病杂志

<p><b>OBJECTIVE</b>To test whether P38 MAPK is involved in angiotensin II (Ang II)-enhanced migration potential of adventitial fibroblasts (AFs) from spontaneously hypertensive rat (SHR).</p><p><b>METHODS</b>Migratory potential was estimated by transwell chamber in vitro. Activation of P38 MAPK pathway was determined with phosphospecific antibodies by immunoblotting.</p><p><b>RESULTS</b>Ang II induced migration of SHR-AFs was markedly increased in a dose-dependent manner when compared with WKY-AFs. Addition of the Ang II receptor type-1 (AT1-R) antagonist Losartan and P38 MAPK inhibitor SB202190 suppressed Ang II-induced migration of SHR-AFs. Ang II could induce P38 MAPK phosphorylation in SHR-AFs in a time-and dose-dependent manner. Phosphorylation of P38 MAPK was suppressed by Losartan and SB202190.</p><p><b>CONCLUSION</b>This study indicated that Ang II-induced migration involves P38 MAPK pathway via AT1 receptor in aortic adventitial fibroblasts from SHR.</p>

A polymorphism of kynureninase gene in a hypertensive candidate chromosomal region is associated with essential hypertension / 中华心血管病杂志

<p><b>OBJECTIVE</b>To identify single nucleotide polymorphisms (SNP) in the regulatory and coding regions of human kynureninase (KYNU) gene in a hypertensive candidate chromosomal region 2q14-q23 of Han Chinese, and to investigate the relationship between polymorphisms in KYNU and essential hypertension.</p><p><b>METHODS</b>The SNPs in the promoter region and exons of the KYNU gene were detected by direct DNA sequencing. Genotyping of the nonsynonymous Lys412Glu (A/G) polymorphism was performed by DHPLC technology in 456 hypertensive patients and 430 normal controls.</p><p><b>RESULTS</b>Sixteen SNP were identified in the KYNU gene, including 6 in the regulatory region and 2 in the coding region (both of them lead to substitution of amino acid). Significant differences between hypertensive patients and normal controls were observed for the distribution of alleles (chi(2) = 6.693, P = 0.035) and genotypes (chi(2) = 4.188, P = 0.041) of the Lys412Glu polymorphism in all subjects, and for the distribution of alleles in the subgroup of men (chi(2) = 4.424, P = 0.035).</p><p><b>CONCLUSION</b>The Lys412Glu polymorphism of the KYNU gene in a hypertensive candidate chromosomal region is associated with essential hypertension in Han Chinese.</p>

Association of peripheral and central blood pressure with the alpha-adducin Gly460Trp polymorphism in a Chinese population / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the association of peripheral and central blood pressure with the alpha-adducin Gly460Trp polymorphism in Chinese.</p><p><b>METHODS</b>We randomly selected 6 villages from JingNing County, ZheJiang Province. We invited nuclear families to take part in our study. We measured each participant's blood pressure at the non-dominant arm by means of a standard mercury sphygmomanometer at subjects' homes. Five consecutive readings were averaged for analysis. Central blood pressures were obtained by use of SphigmoCor pulse wave analysis system. The observers administered a standardized questionnaire to collect information on smoking habits, alcohol consumption and use of antihypertensive drugs. Venous blood was sampled and the adducin genotype was determined by restrictive fragment length polymorphism (RFLP).</p><p><b>RESULTS</b>Four hundred and forty-two subjects included 230 (52.0%) women, and 116 (26.2%) hypertensive patients, of whom 49 (11.1%) took antihypertensive drugs. The frequencies of alpha -adducin GlyGly, GlyTrp and TrpTrp genotypes were 21.3%, 54.5% and 24.2%, respectively. There was no association between the alpha-adducin Gly460Trp polymorphism and peripheral systolic and diastolic blood pressure and pulse pressure. However, both before and after adjustment for sex, age, age(2), body-mass index, current smoking, alcohol intake, and antihypertensive treatment, the alpha-adducin polymorphism was significantly (P < 0.02) associated with central systolic blood pressure and central pulse pressure. After adjustment, central systolic blood pressure (+/- SE) averaged 122.5 +/- 3.5, 114.1 +/- 1.5 and 109.1 +/- 1.8 mm Hg (P = 0.01) in the GlyGly, GlyTrp and TrpTrp subjects, respectively. The corresponding values for central pulse pressure were 39.4 +/- 1.3, 36.4 +/- 1.0 and 32.9 +/- 0.9 mm Hg (P = 0.002), respectively.</p><p><b>CONCLUSIONS</b>In the JingNing population, the adducin 460Trp allele was associated with lower levels of central systolic pressure and pulse pressure.</p>

Association of angiotensin II receptor type 1 gene single nucleotide polymorphism with Chinese essential hypertension complicated with coronary heart disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To identify the genetic variants of angiotensin II type 1 receptor (AT1) gene in a population of Han ethnicity in east China and to determine whether the AT1 gene polymorphisms are associated with essential hypertension (EH) and coronary heart disease (CHD).</p><p><b>METHODS</b>The detection of single nucleotide polymorphisms (SNPs) was performed in 20 subjects by a direct DNA sequencing. All 213 EH patients, 171 patients of EH with CHD and 200 controls were genotyped by three detected SNPs.</p><p><b>RESULTS</b>Eight positive SNPs were detected in the promoter, exon and 3' untranslated region (3'UTR) of AT1 gene. A case-control study by using a frequent SNP (A-153G) in the promoter region, showed a significant increase in allele frequency of G-153 in the subjects of EH complicated with CHD (17.8% vs 11.5% for normal controls, P < 0.05). The SNP A1166C, which has been widely studied, manifested no difference in the three groups.</p><p><b>CONCLUSION</b>A polymorphism in the promoter region (A-153G) of AT1 gene might be involved in the development of EH and CHD in Han ethnicity population in east China.</p>