scholarly journals The Gut Microbiota Is Associated with Vascular Function and Blood Pressure Phenotypes in Overweight and Obese Middle-Aged/Older Adults (P21-024-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Sarah Johnson ◽  
Nicole Litwin ◽  
Hannah Van Ark ◽  
Shannon Hartley ◽  
Emily Fischer ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Arterial Stiffness ◽  
Gut Microbiota ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Reactive Hyperemia ◽  
Bifidobacterium Longum ◽  
Middle Aged ◽  
Principal Coordinates ◽  
The Relationship

Abstract Objectives The gut microbiota is emerging as an important regulator of cardiovascular health. Indeed, gut dysbiosis is increasingly being linked to the development of cardiovascular disease (CVD). Aging and obesity are associated with the development of CVD largely due to the development of vascular dysfunction, namely endothelial dysfunction and arterial stiffness. The objective of this study was to examine the relationship between the gut microbiota, blood pressure, and vascular function in aging overweight and obese individuals. Methods This cross-sectional study included fifteen overweight and obese (mean body mass index, BMI: 29.5; range: 25.8–37.0) middle-aged/older men and postmenopausal women (mean age: 53; range: 42–64 years). Blood pressure, arterial stiffness (augmentation index, AIx, and aortic pulse wave velocity, aPWV), and endothelial function (reactive hyperemia index, RHI) were assessed. Stool samples were collected for gut microbiota analysis using 16S ribosomal RNA sequencing. Principal coordinates analysis and Pearson's correlations were performed to evaluate the relationship between the gut microbiota and measures of vascular function and blood pressure. Results Global gut microbiota phenotypes clustered most strongly by aPWV (groups separated by median value) as visualized by Non-Metric Dimensional Scaling plot of Bray-Curtis Distances (stress = 0.09; P = 0.07). Several bacterial taxa correlated with vascular parameters. For example, Bifidobacterium longum (r = 0.80, P < 0.001) and Akkermansia muciniphila (r = 0.56, P = 0.047) were positively correlated with RHI. Bifdobacterium bifidum (r = −0.61, P = 0.02) and Oxalobacter formigenes (r = −0.62, P = 0.02) were negatively correlated with systolic blood pressure. Interestingly, there was no significant clustering by BMI groupings (overweight vs. obese) or correlations between BMI and specific taxa. Conclusions These preliminary data suggest that the gut microbiota is linked to vascular dysfunction and increased blood pressure in aging overweight and obese individuals independent of BMI. Further data collection and analysis are currently underway to explore these relationships in a larger human cohort, and to explore underlying mechanisms through transferring of vascular phenotypes in humans to germ-free mice through microbiota transplantation. Funding Sources NIFA, USDA.

Abstract P285: Aging In Male Mice Is Characterized By Arterial Stiffening And Diastolic Dysfunction

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Benard O Ogola ◽  
Bruna Visniauskas ◽  
Isabella Kilanowski-doroh ◽  
Caleb M Abshire ◽  
Alec Horton ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Arterial Stiffness ◽  
Cardiac Function ◽  
Vascular Function ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Male Mice ◽  
Middle Aged ◽  
Mature Adult ◽  
Arterial Stiffening

Aging is a nonmodifiable risk factor for cardiovascular mortality and is associated with arterial stiffening and cardiac dysfunction. In this study, we hypothesized that aging would decrease vascular compliance and cardiac function in male mice. Tail-cuff plethysmography was used to measure blood pressure, pulse wave velocity (PWV) for arterial stiffness, echocardiography for systolic and diastolic cardiac function, and wire myography for vessel reactivity in mature adult (25 weeks) and middle-aged (57 weeks) C57Bl/6 mice. Data was analyzed by t-test or 2-way ANOVA, and P<0.05 was considered significant. While there was no difference in blood pressure, PWV was higher in middle-aged male mice (1.8 ± 0.04 m/s vs. 1.2 ± 0.05 m/s; P<0.001) and associated with increased left ventricular (LV) posterior wall thickness (1.4 ± 0.07 mm vs. 1.1 ± 0.13 mm; P=0.03), and LV mass (172 ± 8 mg vs. 158 ± 20 mg; P=0.04). The ratio of early to late filling velocities, a measure of diastolic function, was lower in middle-age (1.6 ± 0.07 vs. 2.7 ± 0.37; P<0.001). Carotid artery histological analysis indicated that middle-aged mice had a greater collagen-to-elastin ratio along with decreased amounts of smooth muscle and thin collagen (P<0.05). Mesenteric artery contraction to PGF2α (446 ± 15% vs. 378 ± 14%; P=0.02) as well as relaxation to sodium nitroprusside (55 ± 7% vs. 31 ± 7%; P<0.01) were both blunted in the middle-aged group. The current study demonstrates that aging in male mice increases arterial stiffening and LV remodeling while decreasing diastolic and vascular function, independent of increased blood pressure. Future studies will investigate whether strategies that counteract arterial stiffness in the absence of changes in blood pressure can protect from cardiovascular aging.

scholarly journals Suppression of gut dysbiosis reverses Western diet-induced vascular dysfunction

2018 ◽  
Vol 314 (5) ◽  
pp. E468-E477 ◽  
Author(s):  
Micah L. Battson ◽  
Dustin M. Lee ◽  
Dillon K. Jarrell ◽  
Shuofei Hou ◽  
Kayl E. Ecton ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Arterial Stiffness ◽  
Gut Microbiota ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Nuclear Factor Κb ◽  
Western Diet ◽  
Standard Diet ◽  
Vascular Abnormalities ◽  
Gut Dysbiosis

Vascular dysfunction represents a critical preclinical step in the development of cardiovascular disease. We examined the role of the gut microbiota in the development of obesity-related vascular dysfunction. Male C57BL/6J mice were fed either a standard diet (SD) ( n = 12) or Western diet (WD) ( n = 24) for 5 mo, after which time WD mice were randomized to receive either unsupplemented drinking water or water containing a broad-spectrum antibiotic cocktail (WD + Abx) ( n = 12/group) for 2 mo. Seven months of WD caused gut dysbiosis, increased arterial stiffness (SD 412.0 ± 6.0 vs. WD 458.3 ± 9.0 cm/s, P < 0.05) and endothelial dysfunction (28% decrease in max dilation, P < 0.05), and reduced l-NAME-inhibited dilation. Vascular dysfunction was accompanied by significant increases in circulating LPS-binding protein (LBP) (SD 5.26 ± 0.23 vs. WD 11 ± 0.86 µg/ml, P < 0.05) and interleukin-6 (IL-6) (SD 3.27 ± 0.25 vs. WD 7.09 ± 1.07 pg/ml, P < 0.05); aortic expression of phosphorylated nuclear factor-κB (p-NF-κB) ( P < 0.05); and perivascular adipose expression of NADPH oxidase subunit p67phox ( P < 0.05). Impairments in vascular function correlated with reductions in Bifidobacterium spp. Antibiotic treatment successfully abrogated the gut microbiota and reversed WD-induced arterial stiffness and endothelial dysfunction. These improvements were accompanied by significant reductions in LBP, IL-6, p-NF-κB, and advanced glycation end products (AGEs), and were independent from changes in body weight and glucose tolerance. These results indicate that gut dysbiosis contributes to the development of WD-induced vascular dysfunction, and identify the gut microbiota as a novel therapeutic target for obesity-related vascular abnormalities.

scholarly journals Blunted peripheral but not cerebral vasodilator function in young otherwise healthy adults with persistent symptoms following COVID-19

2021 ◽  
Author(s):  
Damsara Nandadeva ◽  
Benjamin E. Young ◽  
Brandi Y. Stephens ◽  
Ann-Katrin Grotle ◽  
Rachel J. Skow ◽  
...  
Keyword(s):  
Young Adults ◽  
Arterial Stiffness ◽  
Acute Phase ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Reactive Hyperemia ◽  
Healthy Adults ◽  
Persistent Symptoms ◽  
And Control ◽  
Cerebral Vasodilator

Recent findings suggest that COVID-19 causes vascular dysfunction during the acute phase of the illness in otherwise healthy young adults. To date, no studies have investigated the longer-term effects of COVID-19 on vascular function. Herein, we hypothesized that young, otherwise healthy adults who are past the acute phase of COVID-19 would exhibit blunted peripheral (brachial artery flow-mediated dilation (FMD) and reactive hyperemia) and cerebral vasodilator function (cerebral vasomotor reactivity to hypercapnia; CVMR) and increased central arterial stiffness. Sixteen young adults who were at least 4 weeks past a COVID-19 diagnosis and 12 controls who never had COVID-19 were studied. Eight COVID subjects were symptomatic (SYM) and 8 were asymptomatic (ASYM) at the time of testing. FMD and reactive hyperemia were not different between COVID and Control groups. However, FMD was lower in SYM (3.8 ± 0.6%) compared to ASYM (6.8 ± 0.9%; P = 0.007) and Control (6.8 ± 0.6%; P = 0.003) with no difference between ASYM and Control. Similarly, peak blood velocity following cuff release was lower in SYM (47 ± 8 cm/s) compared to ASYM (64 ± 19 cm/s; P = 0.025) and Control (61 ± 14 cm/s; P = 0.036). CVMR and arterial stiffness were not different between any groups. In summary, peripheral macro- and microvascular function, but not cerebral vascular function or central arterial stiffness were blunted in young adults symptomatic beyond the acute phase of COVID-19. In contrast, those who were asymptomatic had similar vascular function compared to controls who never had COVID.

scholarly journals Gut microbiota from coronary artery disease patients contributes to vascular dysfunction in mice by regulating bile acid metabolism and immune activation

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Honghong Liu ◽  
Ran Tian ◽  
Hui Wang ◽  
Siqin Feng ◽  
Hanyu Li ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Arterial Stiffness ◽  
Gut Microbiota ◽  
Bile Acids ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Bile Acid Metabolism ◽  
Clostridium Symbiosum ◽  
Artery Disease

Abstract Background The gut microbiota was shown to play a crucial role in the development of vascular dysfunction, and the bacterial composition differed between healthy controls and coronary artery disease patients. The goal of this study was to investigate how the gut microbiota affects host metabolic homeostasis at the organism scale. Methods We colonized germ-free C57BL/6 J mice with faeces from healthy control donors (Con) and coronary artery disease (CAD) patients and fed both groups a high fat diet for 12 weeks. We monitored cholesterol and vascular function in the transplanted mice. We analysed bile acids profiles and gut microbiota composition. Transcriptome sequencing and flow cytometry were performed to evaluate inflammatory and immune response. Results CAD mice showed increased reactive oxygen species generation and intensive arterial stiffness. Microbiota profiles in recipient mice clustered according to the microbiota structure of the human donors. Clostridium symbiosum and Eggerthella colonization from CAD patients modulated the secondary bile acids pool, leading to an increase in lithocholic acid and keto-derivatives. Subsequently, bile acids imbalance in the CAD mice inhibited hepatic bile acids synthesis and resulted in elevated circulatory cholesterol. Moreover, the faecal microbiota from the CAD patients caused a significant induction of abnormal immune responses at both the transcriptome level and through the enhanced secretion of cytokines. In addition, microbes belonging to CAD promoted intestinal inflammation by contributing to lamina propria Th17/Treg imbalance and worsened gut barrier permeability. Conclusions In summary, our findings elucidated that the gut microbiota impacts cholesterol homeostasis by modulating bile acids. In addition, the CAD-associated bacterial community was shown to function as an important regulator of systemic inflammation and to influence arterial stiffness.

Abstract P006: Liraglutide Attenuates Cardiac Fibrosis and Vascular Dysfunction in a Non-diabetic Angiotensin II-infusion Model via Anti-inflammatory and Anti-oxidant Mechanisms

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Huey Wen Lee ◽  
Melita Brdar ◽  
Robert Widdop ◽  
Anthony Dear ◽  
Tracey Gaspari
Keyword(s):  
Blood Pressure ◽  
Vascular Function ◽  
Cardiac Fibrosis ◽  
Vascular Dysfunction ◽  
Cardiomyocyte Hypertrophy ◽  
High Dose ◽  
Protective Effects ◽  
Ang Ii ◽  
Treatment Protocols ◽  
Glucose Levels

Glucagon-like peptide-1 (GLP-1) based therapies are used to treat type II diabetes via increasing insulin secretion and inhibiting glucagon production. Recent evidence suggests that activating the GLP-1 receptor may also mediate direct vaso-protective effects. Therefore the objective of the study was to determine whether GLP-1R stimulation conferred cardio- and vaso-protection in a non-diabetic setting using the angiotensin (Ang) II infusion model of hypertension and cardiovascular dysfunction. Male C57Bl/6J mice (4-6 months) were assigned to one of the following 4 week treatment protocols: 1) vehicle (saline), 2) Ang II (800ng/kg/day), 3) Ang II + liraglutide (30μg/kg/day), 4) Ang II + liraglutide (300μg/kg/day). All treatments were administered via osmotic mini-pumps (s.c). After 4 weeks the effect of liraglutide treatment on blood pressure, vascular function and cardiac remodelling was examined. Liraglutide (both doses) attenuated Ang II-induced increase in systolic blood pressure (Ang II: 175.3 ± 8.6mmHg vs Ang II+Lirag (30) 150.2 ± 6.4 mmHg or Ang II+Lirag (300): 145.4 ± 6.9 mmHg) without affecting blood glucose levels. Liraglutide (both doses) completely prevented Ang II-induced endothelial dysfunction (% maximum relaxation: Ang II=50.7 ± 7.8%; Ang II+Lirag (30)=82.7 ± 5.8; Ang II+Lirag (300)=81.5 ± 6.1%). In the heart, liraglutide prevented Ang II-induced cardiomyocyte hypertrophy (n=7-10; p<0.05) and reduced collagen deposition (% collagen expression: Ang II=4.4 ± 0.5 vs Ang II+Lirag(300)=2.9 ± 0.3; n=7-9; p<0.01). This anti-fibrotic effect was attributed to reduced fibroblast/myofibroblast expression as well as decreased inflammation with reduced NFκB and MCP-1 expression and decreased oxidative stress with a significant reduction in superoxide production using high dose of liraglutide. Overall, stimulation of GLP-1R in a non-diabetic setting protected against Ang II-mediated cardiac hypertrophy, cardiac fibrosis and vascular dysfunction, indicating potential for use of GLP-1 based therapies in treatment of cardiovascular disease independent of diabetes.

Abstract 310: Deoxycorticosterone Acetate (doca)-salt Exacerbates Hypertension and Vascular Dysfunction in Mice Expressing Dominant Negative Peroxisome Proliferator-activated Receptor-gamma (pparg) in Smooth Muscle

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Pimonrat Ketsawatsomkron ◽  
Deborah R Davis ◽  
Aline M Hilzendeger ◽  
Justin L Grobe ◽  
Curt D Sigmund
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Transgenic Mice ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Critical Role ◽  
Surrogate Marker ◽  
Dominant Negative ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

PPARG, a ligand-activated transcription factor plays a critical role in the regulation of blood pressure and vascular function. We hypothesized that smooth muscle cell (SMC) PPARG protects against hypertension (HT) and resistance vessel dysfunction. Transgenic mice expressing dominant negative PPARG (S-P467L) in SMC or non-transgenic controls (NT) were implanted with DOCA pellet and allowed ad libitum access to 0.15 M NaCl for 21 days in addition to regular chow and water. Blood pressure was monitored by telemetry and mesenteric arterial (MA) function was assessed by pressurized myograph. At baseline, 24-hour mean arterial pressure (MAP) was similar between NT and S-P467L mice, while the transgenic mice were tachycardic. DOCA-salt increased MAP to a much greater degree in S-P467L mice (Δ MAP; S-P467L: +34.2±6.0, NT: +13.3±5.7, p<0.05 vs NT). Heart rate was similarly decreased in both groups after DOCA-salt. Vasoconstriction to KCl, phenylephrine and endothelin-1 did not differ in MA from DOCA-salt treated NT and S-P467L, while the response to vasopressin was significantly reduced in S-P467L after DOCA-salt (% constriction at 10-8 M, S-P467L: 31.6±5.6, NT: 46.7±3.8, p<0.05 vs NT). Urinary copeptin, a surrogate marker for arginine vasopressin was similar in both groups regardless of treatment. Vasorelaxation to acetylcholine was slightly impaired in S-P467L MA compared to NT at baseline whereas this effect was further exaggerated after DOCA-salt (% relaxation at 10-5 M, S-P467L: 56.1±8.3, NT: 79.4±5.6, p<0.05 vs NT). Vascular morphology at luminal pressure of 75 mmHg showed a significant increase in wall thickness (S-P467L: 18.7±0.8, NT: 16.0±0.4, p<0.05 vs NT) and % media/lumen (S-P467L: 8.4±0.3, NT: 7.1±0.2, p<0.05 vs NT) in S-P467L MA after DOCA-salt. Expression of tissue inhibitor of metalloproteinases (TIMP)-4 and regulator of G-protein signaling (RGS)-5 transcript were 2- and 3.5-fold increased, respectively, in MA of NT with DOCA-salt compared to NT baseline. However, this induction was markedly blunted in S-P467L MA. We conclude that interference with PPARG function in SMC leads to altered gene expression crucial for normal vascular homeostasis, thereby sensitizing the mice to the effects of DOCA-salt induced HT and vascular dysfunction.

scholarly journals The Effect of Long-Term Aronia melanocarpa Extract Supplementation on Cognitive Performance, Mood, and Vascular Function: A Randomized Controlled Trial in Healthy, Middle-Aged Individuals

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2475
Author(s):  
Sanne Ahles ◽  
Yala R. Stevens ◽  
Peter J. Joris ◽  
David Vauzour ◽  
Jos Adam ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cognitive Decline ◽  
Cognitive Performance ◽  
Cognitive Flexibility ◽  
Vascular Function ◽  
Psychomotor Speed ◽  
Middle Aged ◽  
Beneficial Effects ◽  
Aronia Melanocarpa

Cognitive decline is associated with lifestyle-related factors such as overweight, blood pressure, and dietary composition. Studies have reported beneficial effects of dietary anthocyanins on cognition in older adults and children. However, the effect of anthocyanin-rich Aronia melanocarpa extract (AME) on cognition is unknown. Therefore, this study aimed to determine the effect of long-term supplementation with AME on cognitive performance, mood, and vascular function in healthy, middle-aged, overweight adults. In a randomized double-blind placebo-controlled parallel study, 101 participants either consumed 90 mg AME, 150 mg AME, or placebo for 24 weeks. The grooved pegboard test, number cross-out test, and Stroop test were performed as measures for psychomotor speed, attention, and cognitive flexibility. Mood was evaluated with a visual analogue scale, serum brain-derived neurotrophic factor (BDNF) was determined, and vascular function was assessed by carotid ultrasounds and blood pressure measurements. AME improved psychomotor speed compared to placebo (90 mg AME: change = −3.37; p = 0.009). Furthermore, 150 mg AME decreased brachial diastolic blood pressure compared to 90 mg AME (change = 2.44; p = 0.011), but not compared to placebo. Attention, cognitive flexibility, BDNF, and other vascular parameters were not affected. In conclusion, AME supplementation showed an indication of beneficial effects on cognitive performance and blood pressure in individuals at risk of cognitive decline.

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