Hypertension is a serious health problem particularly for African-Americans. Previous studies have suggested that angiotensinogen (AGT) gene locus is involved in human essential hypertension. We have recently shown that an A/G polymorphism at -217 in the promoter of the AGT gene is associated with essential hypertension especially in African-Americans. We report here that A/G polymorphism at -217 affects the glucocorticoid-induced promoter activity of the human AGT gene. We show that recombinant glucocorticoid receptor (GR) binds strongly to the AGT gene promoter when nucleoside A is present at -217, and dexamethasone treatment increases the interleukin 6 induced promoter activity of reporter constructs containing nucleoside A at -217. Similarly cotransfection of GR and C/EBP beta or C/EBP delta increases the promoter activity of reporter construct containing nucleoside A at -217. Since AGT is an acute phase protein, we propose that increased expression of -217A allele of the AGT gene by glucocorticoids and C/EBP family of transcription factors may be involved in essential hypertension.
Angiotensinogen (AGT) is the precursor of one of the most important vasoactive hormone angiotensin II and this gene locus is associated with human essential hypertension. AGT is an acute phase protein and its gene expression is regulated by IL-6. Previous studies have identified three potential STAT-3 binding sites (APREs) located between −160 and −280 of the hAGT gene promoter but only APRE-1 (located between −271 and −279) was shown to be a bonafide enhancer for IL-6-induced promoter activity. We show here that APRE-2, located between −236 and −247, is indeed an HNF-1α-binding site and plays an important role in basal and IL-6 induced promoter activity of this gene. Our chromatin immunoprecipitation (ChIP) assay shows that HNF-1α binds to this region of the hAGT gene promoter and its recruitment is increased in the presence of IL-6 in Hep3B cells. We also show that the promoter activity of a deletion construct containing only 223 bp of the hAGT gene promoter (that contains only APRE-3) is increased after IL-6 treatment. Our ChIP assay shows that IL-6 treatment recruits STAT-3 to APRE-3 and suggests that this is also an IL6 responsive element. We have previously shown that GR binds to the proximal promoter of the hAGT gene. Since GR physically interacts with STAT-3, we propose that transcription factors GR, STAT-3, and HNF-1α that bind to the nucleotide sequence located between −160 and −280 of the hAGT gene promoter are responsible for IL-6 induced promoter activity of this gene.
1. Hypertension is a serious risk factor for myocardial infarction, heart failure, vascular disease, stroke and renal failure. The incidence of hypertension is 25-30% in the adult Caucasian population and complications due to hypertension are even greater in African Americans. 2. The renin-angiotensin system plays an important role in the regulation of blood pressure and previous studies have suggested that angiotensinogen (AGT) gene locus is linked with human essential hypertension. Earlier studies suggested that a single nucleotide polymorphism (SNP) that converts methionine to threonine at amino acid 235 is associated with hypertension in the Caucasian population. However, this SNP is not associated with hypertension in African American and Chinese populations. 3. We have found an A/G polymorphism at -217 of the human AGT gene promoter and have shown that the frequency of allele A at -217 is significantly increased in the genomic DNA of African American hypertensive patients. 4. We have also shown that: (i) reporter constructs containing the AGT gene promoter with nucleoside A at -217 have increased promoter activity on transient transfection; and (ii) the CCAAT box enhancer binding protein (C/EBP) family of transcription factors and glucocorticoid receptor (GR) bind preferentially to this region of the promoter when nucleoside A is present at -217. In addition, variant -217A is always present with variants -532T, -793A and -1074T in the human AGT gene promoter. 5. These data suggest that the AGT haplotype containing -217A, -532T, -793A and -1074T may be involved in increased transcription of this gene and may play a role in human hypertension.
Context: Hypertension (HTN) has been gaining more importance, due to rising apprehension of its causative func- tion in cardiovascular complications like stroke, coronary artery disease. Blood Pressure Management Program (BPMP) is a combination of Panchakarma and allied therapies and herbal drug therapy. Aim: This study was conducted to evaluate the effect of BPMP on systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), body mass index (BMI) and dependency on conventional therapy in HTN Patients. Settings and Design: This retrospective study was conducted in July 2017, wherein the data of HTN patients who attended out-patient departments (OPDs) at Madhavbaug clinics in Pune, Maharashtra, India were identified. Methods and Material: Data of patients who were administered BPMP (60-75 minutes) with a minimum of 6 sittings over 90 days (± 15 days) were considered. Variables were compared between day 1 and day 90 of BPMP. Statistical analysis Used: Data were pooled and coded in a Microsoft Excel spreadsheet. R Version 3.4.1 software was used to analyse the data. Results: Out of 30 enrolled patients, 28 were males while 2 were females. BPMP showed significant improvement in SBP by 19.22% (from 144.73 ± 15.54 to 121.4 ± 14.34; p<0.001), DBP by 14.34% (from 86.06± 9.94 to 75.26 ± 6.35, p< 0.001), MAP by 17.31% (from 105.82 ± 11.20 to 90.20 ± 6.40, p<0.001). BMI (26.36 ± 3.38 kg/m2 to 25.59 ± 3.07 kg/m2), also showed significant reduction. Dependency on concomitant medicines was reduced, with the number of patients on no concomitant medicines increasing from 13% to 30%. Conclusions: BPMP can be an effective option for the management of HTN patients, along with conventional allopathic medications. Keywords: Blood pressure management program, BPMP, Panchakarma, Hypertension, Blood pressure, Systolic, Diastolic, Mean arterial pressure, Alternative medicine.
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