Patterns of lipid profile abnormalities in hypertensive patients and normotensive subjects: a cross-sectional observational study

Background: It is a well-known fact that hypertension and altered lipid profile or dyslipidaemia are leading risk factors for cardiovascular diseases. The coexistence of these two conditions has remained an interesting matter, among cardiologists and researchers alike. In this study, we analysed the serum lipid patterns of hypertensive patients and normotensive control subjects.Methods: This cross-sectional observational study was conducted in a tertiary healthcare and teaching center of Northwestern India during the period of 2010 and 2011. The study comprised of 100 hypertensive patients and 100 normotensive control subjects. Data were collected regarding demographic details, past medical/drug history and lipid profile including total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high-density lipoprotein (HDL).Results: A total of 200 subjects with the age above 20 years were enrolled in the study. The mean BMI in hypertensive patients (24.14±2.15 kg/m2) was significantly higher than normotensive subjects (22.60±2.62 kg/m2) (p<0.05). When we compared the mean of TC and TG among the hypertensive patients and normotensive subjects, highly significant differences were obtained (p<0.001). The significant decline in mean HDL level was observed in hypertensive patients than normotensive subjects (40.41±4.57 versus 44.64±5.97, p<0.005).Conclusions: The dyslipidaemia has been more evident among hypertensive patients. Hence, the measurement of blood pressure and lipid profile are of great importance to prevent cardiovascular diseases, stroke and other comorbidities.

Increased Intraocular Pressure in Glaucomatous, Ocular Hypertensive, and Normotensive Space Shuttle Crew

BACKGROUND: Glaucoma and ocular hypertension (OHT) are prevalent diseases with baseline intraocular pressure (IOP) elevations that future astronauts and spaceflight participants may suffer from. Preflight, in-flight, and postflight IOP measurements were collected aboard two U.S. Space Shuttle Program missions in normotensive control, OHT, and glaucomatous crewmembers. METHODS: Five subjects (three controls, one glaucomatous, one OHT) were studied aboard 2-wk Space Shuttle missions. Baseline IOP (triplicate; handheld tonometry) was recorded during training 12 mo preflight, in flight (114 d), and postflight (329 d). Subjective symptoms were recorded via questionnaires. Data were analyzed using a spreadsheet with two-sample t-tests. P-value < 0.05 determined significance. RESULTS: IOP increased for all in-flight vs. preflight measurements for controls (N 3, 48.9, 16.9, 5.85), OHT (N 1, 20.3), and glaucomatous (N 1, 32.2) groups. IOP eventually returned to baseline postflight [Return (R)35 d], except for the astronaut with OHT (R917). Subjective symptoms, likely multifactorial, included blurredvision, decreased visual acuity, and headaches. DISCUSSION: IOP increased during spaceflight and normalized upon return. Astronauts and commercial spaceflight participants may need screening for elevated IOP to potentially prevent sequelae related to glaucoma and OHT, the former which requires treatment in flight and the latter which may need prophylaxis. Previous studies have shown elevated IOP upon entry into microgravity with various normalization timeframes in flight and postflight. It is unclear how increased IOP relates to spaceflight-associated neuro-ocular syndrome (SANS); however, several hypotheses exist. Treatment strategies should be available for acute and chronic ocular pathology during spaceflight despite the unique challenges of eye-drop application in microgravity. Dalal SR, Ramachandran V, Khalid R, Manuel FK, Knowles JR, Jones JA. Increased intraocular pressure in glaucomatous, ocular hypertensive, and normotensive space shuttle crew. Aerosp Med Hum Perform. 2021; 92(9):728733.

Decreased expression of annexin A2 and loss of its association with vascular endothelial growth factor leads to the deficient trophoblastic invasion in preeclampsia

Objectives Preeclampsia (PE) remains the major cause for maternal and foetal mortality and morbidity. Invasion of endovascular trophoblast and remodelling of spiral artery are crucial actions of normal placental development. Non-fulfilment of these processes plays a leading role in the development of preeclampsia. Vascular endothelial growth factor (VEGF) is produced by extravillous trophoblastic tissue and decidual cell population is a well-known angiogenic growth which plays a fundamental role in placental pathogenesis of PE. Annexin A2 (ANXA2) is a profibrinolytic protein receptor required for plasminolysis, which is an important step in the formation of new blood vessel along with VEGF. Role of ANXA2 is poorly studied in context with human reproductive disease like preeclampsia. The purpose of the present study is to examine the expression and association of VEGF and ANXA2 in the term placentas of pregnancies with and without PE. Methods The study group comprised of placental tissues procured from gestations with PE (n=30) and without (n=20) PE. The expression of VEGF and ANXA2 in the placental villous tissue was evaluated quantitatively by means of IHC, western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR). Results Our IHC, western blotting and RT-PCR analysis illustrated the significant decrease in the expression of VEGF and ANXA2 in PE group compared with the normotensive control group (p<0.005). We observed statistically significant positive correlation among the expression of ANXA2 and VEGF in placentas of normotensive control group (p<0.0001). Conclusions The diminished expression of VEGF and ANXA2 in placenta may be associated with the defective angiogenesis and which may possibly play a vital role in PE pathogenesis.

Placental Genetic Variants in the Upstream Region of the FLT1 Gene in Pre-eclampsia

Background: Soluble fms-like tyrosine kinase 1 (sFlt-1) is believed to be a prominent component in the pathogenesis of pre-eclampsia, although the precise etiology has remained elusive. In this study, the etiological role of FLT1 variant was further validated in pre-eclampsia by examining this association in a Japanese sample population. Methods: The genotypes of three variants (rs4769613, rs12050029 and rs149427560) were examined in the upstream region of the FLT1 gene in placentas from pre-eclamptic (n=47) or normotensive control (n=49) pregnancy samples. Additionally, FLT1 mRNA levels in placenta were determined by qRT-PCR. ELISA was further used to detect circulating sFlt-1 levels in maternal sera. The intergroup comparisons were made using the Mann-Whitney U test or one way analysis of variance and P values of less than 0.05 were considered statistically significant. Results: First, the rs4769613 (C>T) and rs12050029 (G>A) genotypes were examined in placentas but no significant differences were found in the genotype or allele-type frequencies. Next, nearby short tandem repeat, rs149427560, was examined which manifested four size variants. In the genotypewise analysis, the frequency of the 474/476 heterozygote was significantly lower in pre-eclampsia (p<0.05). As expected, the FLT1 mRNA levels were significantly elevated in the pre-eclamptic placentas and sFlt-1 was higher in pre-eclamptic maternal sera. However, the genotype of these variants did not affect the FLT1 mRNA or serum sFlt-1 levels. Conclusion: Our findings did not support the hypothesis that genetic variations around the FLT1 gene affect the subtle expression changes underlying the etiologic pathway of pre-eclampsia. The hypothesis deserves further investigation through a larger sample size.

Abstract P141: Immunosuppressant Treatment Attenuates Augmentation Of Intrarenal NLRP-3 Inflammasome In Angiotensin II-dependent Hypertension

Activated inflammasomes enhance maturation of pro-inflammatory cytokines, which facilitates the development of kidney injury. NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), one of major subunits in the inflammasome complex, plays a crucial role in innate immunity and inflammation. Although NLRP3 inflammasome is activated by ATP-P2Y7 axis and reactive oxygen species, the expression of pro-NLRP3 is promoted by NF-κB activated by cytokines or PAMPs/DAMPs. Thus, we hypothesized that mycophenolate mofetil (MMF), an immunosuppressant, attenuates augmentation of intrarenal NLRP3 and consequent progression of kidney injury in angiotensin II (Ang II)-dependent hypertension. Ang II (80 ng/min) was infused with/without daily MMF administration (50 ng/kg) to Sprague-Dawley rats for 2 weeks. mRNA levels of intrarenal NLRP3 and AIM2, which forms another type of inflammasome complex by viral or bacterial infections, were measured by droplet digital PCR. Furthermore, kidney injury was evaluated. MMF treatment mitigated Ang II-induced macrophage infiltration into kidneys, suggesting immunosuppression by the drug. Ang II infusion significantly increased intrarenal NLRP3 mRNA levels (normotensive control group: 4.12±1.1 copies/ng RNA vs. Ang II-infused group: 9.96±1.8 copies, N=5). The elevated NLRP3 expression in kidneys of Ang II-infused rats was attenuated by MMF treatment (6.24±1.4 copies). In contrast, intrarenal AIM2 levels were lower than NLRP3 in the control group and the levels were not altered by Ang II infusion or MMF treatment (normotensive control group: 0.42±0.1 copies, Ang II-infused group: 0.35±0.06 copies and Ang II+MMF group: 0.35±0.08 copies). Urinary protein and angiotensinogen levels were elevated in Ang II-infused rats and MMF treatment suppressed the augmentations. Histological analyses also showed the development of kidney injury including mesangial expansion and tubulointerstitial fibrosis observed in the hypertensive rats, but these injury markers were mitigated by MMF. These results demonstrate activation of the NLRP3 inflammasome in Ang II dependent hypertension and indicate that immunosuppression by MMF mitigates the inflammasome activation, which contributes to attenuation of the kidney injury.

The Effects of Salt and Glucose Intake on Angiotensin II and Aldosterone in Obese and Nonobese Patients with Essential Hypertension

Background. The exact mechanisms for the development of essential hypertension are not known. Activation of the renin-angiotensin-aldosterone system (RAAS) in adipose tissue may represent an important link between obesity and hypertension. This study investigates the effects of oral intake of glucose with and without NaCl on angiotensin II (AngII) and aldosterone in obese and nonobese patients with essential hypertension. Methods. Twenty newly diagnosed untreated essential hypertensive patients and 15 normotensive control subjects matched for age, gender, and BMI were studied. Participants fasted overnight (8–10 hrs), and then each subject took 75 gm glucose alone and with 3 gm NaCl, each dissolved in 250 ml. Subjects were monitored for 2 hours. Half hourly BP, plasma glucose (PG), serum Na+, K+, insulin, AngII, and aldosterone were measured. Subjects were classified into obese (BMI >30 Kg/m2) (11 patients and 8 control) and nonobese (BMI <30 Kg/m2) (9 patients and 7 control). Results. After intake of glucose with NaCl serum, AngII was significantly higher in obese hypertensive patients compared with nonobese patients (P=0.016). Intake of glucose with NaCl resulted in a significantly higher serum Na in obese hypertensive patients compared with nonobese patients Na (P=0.009). Serum aldosterone was significantly higher in obese patients (P=0.03, after glucose; P=0.003, after glucose with NaCl) and in nonobese patients (P=0.000 and P=0.000, respectively) compared with their respective normotensive control subjects. In obese and nonobese patients, intake of glucose and glucose with NaCl showed no significant change in the levels of serum AngII and aldosterone which was associated a significant increase in serum Na in obese patients (P=0.03) and a highly significant reduction in serum K in nonobese patients (P=0.001). Conclusion. Failure of suppression or inappropriate maintenance of secretion of AngII and aldosterone in both hypertensive groups by intake of glucose with NaCl may indicate a possible mechanism of essential hypertension.

Genome-Wide Association Study of Apparent Treatment-Resistant Hypertension in the CHARGE Consortium: The CHARGE Pharmacogenetics Working Group

BACKGROUND Only a handful of genetic discovery efforts in apparent treatment-resistant hypertension (aTRH) have been described. METHODS We conducted a case–control genome-wide association study of aTRH among persons treated for hypertension, using data from 10 cohorts of European ancestry (EA) and 5 cohorts of African ancestry (AA). Cases were treated with 3 different antihypertensive medication classes and had blood pressure (BP) above goal (systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg) or 4 or more medication classes regardless of BP control (nEA = 931, nAA = 228). Both a normotensive control group and a treatment-responsive control group were considered in separate analyses. Normotensive controls were untreated (nEA = 14,210, nAA = 2,480) and had systolic BP/diastolic BP &lt; 140/90 mm Hg. Treatment-responsive controls (nEA = 5,266, nAA = 1,817) had BP at goal (&lt;140/90 mm Hg), while treated with one antihypertensive medication class. Individual cohorts used logistic regression with adjustment for age, sex, study site, and principal components for ancestry to examine the association of single-nucleotide polymorphisms with case–control status. Inverse variance-weighted fixed-effects meta-analyses were carried out using METAL. RESULTS The known hypertension locus, CASZ1, was a top finding among EAs (P = 1.1 × 10−8) and in the race-combined analysis (P = 1.5 × 10−9) using the normotensive control group (rs12046278, odds ratio = 0.71 (95% confidence interval: 0.6–0.8)). Single-nucleotide polymorphisms in this locus were robustly replicated in the Million Veterans Program (MVP) study in consideration of a treatment-responsive control group. There were no statistically significant findings for the discovery analyses including treatment-responsive controls. CONCLUSION This genomic discovery effort for aTRH identified CASZ1 as an aTRH risk locus.

MARcKS and nAP-22 proteins mRnA expression in renal cortex and renal medulla of rats with spontaneous hypertension

Objective. To study the changes in mRNA expression level of two main protein kinase C substrates — MARCKS and NAP-22 — in rats with spontaneous hypertension (SHR rats) and in normotensive control rats (WKY rats) in renal cortex, renal medulla and total kidney. We also aimed at the identification of possible interstrain differences between the mRNA expression levels.Design and methods.We assessed the level of MARCKS and NAP-22 mRNA by real-time polymerase chain reaction in male SHR and WKY (as a normotensive control) rats.Results. In SHR rats, MARCKS mRNA expression level in renal cortex was 1,5 times higher than in renal medulla (p = 0,0001) and also higher than in total kidney (p = 0,001), in renal medulla it was lower than in total kidney (p = 0,002). In WKY rats, MARCKS mRNA expression level in renal cortex was higher than in renal medulla (p = 0,0005). There was no differences neither between renal cortex and total kidney (p = 0,011), nor between renal medulla and total kidney (p = 0,716). In SHR rats, NAP-22 mRNA expression level in renal cortex was twofold higher than in renal medulla (p = 0,001), in renal medulla it was lower than in total kidney (p = 0,005), the differences between renal cortex and total kidney were less significant (p = 0,011). In WKY rats, NAP-22 mRNA expression level in renal cortex was 1,5 times higher than in renal medulla (p = 0,001), while in renal medulla it was lower than in total kidney (p = 0,002). There was no significant difference in NAP-22 mRNA expression level between renal medulla and total kidney (p = 0,011). There were no significant interstrain differences in the animal groups either in the levels of MARCKS mRNA expression in renal cortex (p = 0,872), in renal medulla (p = 0,024) or in total kidney (p = 0,520). Neither there were differences in the levels of NAP-22 mRNA expression in cortex (p = 0,028), in medulla (p = 0,028) and in total kidney (p = 0,978).Conclusions. In both SHR and WKY rat strains, the level of MARCKS and NAP-22 mRNA expression in cortical and medullary kidney layers is different, in WKY rats these differences are less pronounced. At the same time, interstrain differences in NAP-22 and MARCKS mRNA expression levels in cortical, medullary layers and in total kidney of SHR and WKY rats were not found.

Evaluation of Antihypertensive Effect of Fruit Beverage of Crataegus crenulata Roxb. : A wild Shrub of Himalayan Hills

<p>Morphological and biochemical studies of <em>Crataegus crenulata</em> syn.<em> Pyracantha crenulata</em> fruits have been carried out and an herbal formulation was prepared from its fruit juice. The small sized berries weighing 250 mg each and 4000±32 fruits in 1kg weight contain 25% fruit juice. Biochemical analysis of fruit juice quantified flavonoides content (2-3%), Vitamin ‘A’ (289 IU/ 100g), vitamin B₁₂ (110 µg/100g), Vitamin ‘C’ (57.8mg/100g), Vitamin ‘E’ (289mg/100g) protein (1.6%), calcium (3.79 mg/100g), magnesium (1.38 mg/100g), and potassium (1.39mg/100g). The present study was designed to investigate the efficacy of the herbal formulation from <em>C. crenulata</em> fruits in two forms of experimental hypertension: cadmium chloride induced and in normotensive control in animal module. Since the blood pressure fells down independently in the hypertensive and normotensive rats, the study strongly suggested <em>C. crenulata </em>possesses anti-hypertensive or hypotensive effects.</p>