Abstract P170: Similarities And Differences In The Vascular Impact Of Estrogen Loss Versus G Protein-coupled Estrogen Receptor Deletion

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Isabella M Kilanowski-Doroh ◽  
Tristen J Wong ◽  
Benard O Ogola ◽  
Nicholas Harris ◽  
Alec Horton ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Estrogen Receptor ◽  
Smooth Muscle ◽  
Arterial Stiffness ◽  
G Protein ◽  
Vascular Stiffness ◽  
Area Fraction ◽  
Increased Risk ◽  
The Impact ◽  
G Protein Coupled

Women in their postmenopausal years have an increased risk of cardiovascular disease, and recent research suggests that increased vascular stiffness can be detected within a year of the onset of menopause. We have previously demonstrated that the G Protein-Coupled Estrogen Receptor (GPER) protects the vasculature without noticeable changes in blood pressure, but little is known about the underlying structural changes that provide protection. In this study we assessed the impact of estrogen and the G protein-coupled estrogen receptor (GPER) on vascular health, with the hypothesis that loss of estrogen or deletion of smooth muscle cell (smc)-GPER would similarly increase vascular stiffness. Female mice were separated into three cohorts: intact wildtype, ovariectomized (OVX), and GPER smc-KO. OVX occurred at 8 weeks of age and 8 weeks later blood pressure was measured via tail-cuff plethysmography, arterial stiffness was measured as pulse wave velocity (PWV) via high resolution ultrasound, and carotids were excised for biaxial pressure myography and imaging. Uterine weight in OVX mice (0.03 g) was significantly lower than intact mice (0.1 g; p=0.0002) confirming the loss of estrogen. No difference was observed in systolic blood pressure, however, both the OVX (1.5 m/s) and smc-KO (1.9 m/s) groups had significantly higher PWV than intact controls (1.2 m/s; p=0.02 and p=0.03, respectively). Carotids of OVX (366 μm) and smc-KO (389 μm) mice had a smaller outer diameter versus controls (441 μm; p >0.05) without a difference in thickness. Despite the similar responses of OVX and smc-KO groups, Masson’s trichrome staining of carotid sections showed significantly more smooth muscle area fraction in OVX (p=0.005), but not KO mice, and no difference in collagen area fraction. These data indicate that while estrogen loss and smc-KO of GPER both increase arterial stiffness, increased smooth muscle due to estrogen loss is likely not modulated through GPER. Future experiments will aim to understand how other components, such as extracellular matrix genes, may be affected by loss of GPER.

scholarly journals The G Protein-Coupled Estrogen Receptor 1 (GPER1/GPR30) Agonist G-1 Regulates Vascular Smooth Muscle Cell Ca2+Handling

2013 ◽  
Vol 50 (5) ◽  
pp. 421-429 ◽  
Author(s):  
Anders Holm ◽  
Per Hellstrand ◽  
Björn Olde ◽  
Daniel Svensson ◽  
L.M. Fredrik Leeb-Lundberg ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
G Protein ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
G Protein Coupled ◽  
Estrogen Receptor 1

scholarly journals Activation of G Protein-Coupled Estrogen Receptor 1 Ameliorates Proximal Tubular Injury and Proteinuria in Dahl Salt-Sensitive Female Rats

2021 ◽  
Author(s):  
Eman Y Gohar ◽  
Rawan N Almutlaq ◽  
Elizabeth M. Daugherty ◽  
Maryam K. Butt ◽  
Chunhua Jin ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Estrogen Receptor ◽  
Proximal Tubule ◽  
G Protein ◽  
Brush Border ◽  
Kidney Injury ◽  
Female Rats ◽  
Independent Manner ◽  
G Protein Coupled ◽  
Estrogen Receptor 1

Recent evidence indicates a crucial role for G protein-coupled estrogen receptor 1 (GPER1) in the maintenance of cardiovascular and kidney health in females. The current study tested whether GPER1 activation ameliorates hypertension and kidney damage in female Dahl salt-sensitive (SS) rats fed a high-salt (HS) diet. Adult female rats were implanted with telemetry transmitters for monitoring blood pressure and osmotic minipumps releasing G1 (selective GPER1 agonist, 400 μg/kg/day, intraperitoneal) or vehicle. Two weeks after pump implantation, rats were shifted from a normal salt diet (NS, 0.4% NaCl) to a matched HS diet (4.0% NaCl) for 2 weeks. 24-hour urine samples were collected during both diet periods and urinary markers of kidney injury were assessed. Histological assessment of kidney injury was conducted after the 2-week HS diet period. Compared with values during the NS diet, 24-hour mean arterial pressure markedly increased in response to HS, reaching similar values in vehicle-treated and G1-treated rats. HS also significantly increased urinary excretion of protein, albumin, nephrin (podocyte damage marker) and KIM-1 (proximal tubule injury marker) in vehicle-treated rats. Importantly, G1 treatment prevented the HS-induced proteinuria, albuminuria and increase in KIM-1 excretion but not nephrinuria. Histological analysis revealed that HS-induced glomerular damage did not differ between groups. However, G1 treatment preserved proximal tubule brush border integrity in HS-fed rats. Collectively, our data suggest that GPER1 activation protects against HS-induced proteinuria and albuminuria in female Dahl SS rats by preserving proximal tubule brush border integrity in a blood pressure-independent manner.

scholarly journals A hypertension patient-derived iPSC model demonstrates a role for G protein-coupled estrogen receptor in hypertension risk and development

2020 ◽  
Vol 319 (5) ◽  
pp. C825-C838 ◽  
Author(s):  
Natalie C. Fredette ◽  
Eliyah Malik ◽  
Marah L. Mukhtar ◽  
Eric R. Prossnitz ◽  
Naohiro Terada
Keyword(s):  
Endothelial Cells ◽  
Estrogen Receptor ◽  
G Protein ◽  
Vascular Endothelial Cells ◽  
Association Studies ◽  
No Production ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Increased Risk ◽  
G Protein Coupled

Hypertension (HTN) is a polyfactorial disease that can manifest severe cardiovascular pathologies such as heart failure or stroke. Genome-wide association studies (GWAS) of HTN indicate that single-nucleotide polymorphisms (SNPs) contribute to increased risk for HTN and resistance to some HTN drug regimens (Hiltunen TP et al., J Am Heart Assoc 4: e001521, 2015; Le MT et al., PLoS One 8: e52062, 2013; McDonough CW et al., J Hypertens 31: 698–704, 2013; Vandell AG et al., Hypertension 60: 957–964, 2012). However, cellular mechanistic insights of such SNPs remain largely unknown. Using a bank of induced pluripotent stem cells (iPSCs) derived from patients with HTN and CRISPR/Cas9-mediated gene-editing approach, we investigated the effects of a female HTN risk-associated SNP (rs1154431) of the G protein-coupled estrogen receptor (GPER) (Bassuk SS, Manson JE., Clin Chem 60: 68–77, 2014) in vascular endothelial cells. Although GPER1 deletion reduced endothelial nitric oxide synthase (eNOS) activation in iPSC-derived endothelial cells (iECs), the polymorphism itself did not significantly affect eNOS and NO production in a comparison of isogenic hemizygous iECs expressing either normal (P16) or HTN-associated (L16) GPER. Interestingly, we demonstrate for the first time that GPER plays a role in regulation of adhesion molecule expression and monocyte adhesion to iECs. Moreover, the L16 iECs had higher expression of inflammation genes than P16 iECs, implying that the risk variant may affect carrier individuals through increased inflammatory activity. This study further indicates that iPSCs are a useful platform for exploring mechanistic insights underlying hypertension GWAS endeavors.

scholarly journals The Impact of Valsartan/Amlodipine Single-Pill Combination on Blood Pressure and Vascular Stiffness in Patients with Grade 1-2 Essential Arterial Hypertension

2019 ◽  
Vol 14 (6) ◽  
pp. 831-839
Author(s):  
E. V. Borisova ◽  
A. I. Kochetkov ◽  
O. D. Ostroumova
Keyword(s):  
Blood Pressure ◽  
Arterial Stiffness ◽  
Arterial Hypertension ◽  
Antihypertensive Therapy ◽  
Vascular Stiffness ◽  
Stage Ii ◽  
Ambulatory Bp Monitoring ◽  
Single Pill ◽  
Essential Arterial Hypertension ◽  
The Impact

Aim. To investigate the impact of valsartan/amlodipine single-pill combination (V/A SPC) on arterial stiffness parameters and 24-hours blood pressure (BP) level in the middle-aged patients with stage II grade 1-2 essential arterial hypertension (HT). Material and methods. A group of patients with stage II grade 1-2 HT who had not previously received regular antihypertensive therapy (n=38, age 49.7±7.0 years) was retrospectively formed. All the patients were treated with V/A SPC and all of them achieved target office BP (<140/90 mm Hg). 12 weeks after reaching the target BP the assessment of V/A SPC therapy effectiveness and vascular stiffness (general clinical data, ambulatory BP monitoring, volume sphygmography, echocardiography) were performed in all included HT patients. Sex- and age-matched healthy people with normal BP (n=86, age 48.8±5.8years) and in whom similar clinical and vascular stiffness data were available represented a control group. Results. According to the ambulatory BP monitoring data systolic, diastolic and pulse BP significantly (p<0.001) decreased after the treatment with V/A SPC. Volume sphygmography has showed significant decrease in right-CAVI value from 8.9±1.3 to 7.3±1.4 (p=0.021) as well as a reduction the number of patients with a right- and/or left-CAVI>9.0 from 31.6 to 10.5% (p=0,049). According to an assessment of arterial stiffness the augmentation index decreased significantly by 23.6±8.6% from -23.0±17.1 to -28.9±18.7 (p=0.034. Transthoracic echocardiography data has demonstrated decrease in effective arterial elastance from 1.73±0.35 to 1.60±0.32 mm Hg (p=0.016) and increase in the arterial compliance – from 1.30±0.38 to 1.43±0.34 mm Hg/ml (p=0.049). Conclusions. In naive patients 40-65 years old with stage II grade 1-2 HT antihypertensive therapy with V/A SPC provides effective 24 hours BP control and improves arterial stiffness parameters.

scholarly journals Sex and the G Protein–Coupled Estrogen Receptor Impact Vascular Stiffness

Hypertension ◽  
2021 ◽  
Author(s):  
Benard O. Ogola ◽  
Gabrielle L. Clark ◽  
Caleb M. Abshire ◽  
Nicholas R. Harris ◽  
Kaylee L. Gentry ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Estrogen Receptor ◽  
Sex Differences ◽  
G Protein ◽  
Wall Thickness ◽  
Left Ventricular ◽  
Axial Stiffness ◽  
Ang Ii ◽  
Wild Type ◽  
G Protein Coupled

Because arterial stiffness increases following menopause, estrogen may be a protective factor. Our previous work indicates that the GPER (G protein–coupled estrogen receptor) mediates estrogen’s vascular actions. In the current study, we assessed arterial stiffening using pulse wave velocity (PWV), a clinically relevant measurement that independently predicts cardiovascular mortality. We hypothesized that genetic deletion of GPER would attenuate sex differences in PWV and would be associated with changes in passive vascular mechanics. Control and Ang II (angiotensin II)–infused male and female wild-type and GPER knockout mice were assessed for blood pressure, intracarotid PWV, cardiac function, passive biaxial mechanics, constitutive modeling, and histology. Sex differences in PWV and left ventricular mass were detected in wild-type mice but absent in GPER knockout and Ang II–infused mice, regardless of genotype. Despite lower PWV, the material stiffness of female wild-type carotids was greater than males in control conditions and was maintained in response to Ang II due to increased wall thickness. PWV positively correlated with unloaded thickness as well as circumferential and axial stiffness only in females. In contrast, blood pressure positively associated with circumferential and axial stiffness in males. Taken together, we found that female wild-type mice were unique in their vascular adaptation to hypertension by increasing wall thickness to maintain stiffness. Given that carotid arteries are easily accessible clinically, systematic assessment of intracarotid PWV in women may provide insight into vascular damage that cannot be assumed from blood pressure measurements alone.

scholarly journals Olfactory receptor Olfr78 (prostate-specific G protein-coupled receptor PSGR) expression in arterioles supplying skeletal and cardiac muscles and in arterioles feeding some murine organs

2021 ◽  
Author(s):  
Petra Mermer ◽  
Jörg Strotmann ◽  
Wolfgang Kummer ◽  
Renate Paddenberg
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
G Protein ◽  
Olfactory Receptor ◽  
Muscle Cells ◽  
Striated Muscles ◽  
Pressure Regulation ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

AbstractThe olfactory receptor Olfr78 (prostate-specific G protein-coupled receptor PSGR) is a member of the G protein-coupled receptor family mediating olfactory chemosensation, but it is additionally expressed in other tissues. Olfr78 expressed in kidney participates in blood pressure regulation, and in prostate it plays a role in the development of cancer. We here screened many organs/tissues of transgenic mice co-expressing β-galactosidase with Olfr78. X-gal-positive cells were detectable in smooth muscle cells of numerous arterioles of striated muscles (heart ventricles and skeletal muscles of various embryological origin). In addition, in most organs where we found expression of Olfr78 mRNA, X-gal staining was restricted to smooth muscle cells of small blood vessels. The dominant expression of Olfr78 in arteriolar smooth muscle cells supports the concept of an important role in blood pressure regulation and suggests a participation in the fine tuning of blood supply especially of striated muscles. This should be considered when targeting Olfr78 in other contexts such as prostate cancer.

Abstract 113: Female Protection From Arterial Stiffness Diminishes With G Protein-Coupled Estrogen Receptor Deletion or Angiotensin II Hypertension

Hypertension ◽  
2018 ◽  
Vol 72 (Suppl_1) ◽  
Author(s):  
Benard O Ogola ◽  
Caleb M Abshire ◽  
Gabrielle L Clark ◽  
Dylan J Lawrence ◽  
Margaret A Zimmerman ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Angiotensin Ii ◽  
Arterial Stiffness ◽  
G Protein ◽  
G Protein Coupled
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