scholarly journals Vascular Aging across the Menopause Transition in Healthy Women

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Kerrie L. Moreau ◽  
Kerry L. Hildreth
Keyword(s):  
Endothelial Dysfunction ◽  
Postmenopausal Women ◽  
Endurance Exercise ◽  
Ovarian Function ◽  
Future Research ◽  
Large Artery ◽  
Vascular Aging ◽  
Age Related ◽  
Artery Stiffness ◽  
Menopause Transition

Vascular aging, featuring endothelial dysfunction and large artery stiffening, is a major risk factor for developing cardiovascular disease (CVD). In women, vascular aging appears to be accelerated during the menopause transition, particularly around the late perimenopausal period, presumably related to declines in ovarian function and estrogen levels. The mechanisms underlying endothelial dysfunction and large artery stiffening with the menopause transition are not completely understood. Oxidative stress and the proinflammatory cytokine tumor necrosis factor-α contribute to endothelial dysfunction and large artery stiffening in estrogen-deficient postmenopausal women. Habitual endurance exercise attenuates the age-related increase in large artery stiffness in estrogen-deficient postmenopausal women and can reverse arterial stiffening to premenopausal levels in estrogen-replete postmenopausal women. In contrast, estrogen status appears to play a key permissive role in the adaptive response of the endothelium to habitual endurance exercise in that endothelial improvements are absent in estrogen-deficient women but present in estrogen-replete women. We review here the current state of knowledge on the biological defects underlying vascular aging across the menopause transition, with particular focus on potential mechanisms, the role of habitual exercise in preserving vascular health, and key areas for future research.

scholarly journals Inorganic nitrite supplementation for healthy arterial aging

2014 ◽  
Vol 116 (5) ◽  
pp. 463-477 ◽  
Author(s):  
Amy L. Sindler ◽  
Allison E. DeVan ◽  
Bradley S. Fleenor ◽  
Douglas R. Seals
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Therapeutic Potential ◽  
Vascular Dysfunction ◽  
Aortic Pulse Wave Velocity ◽  
Vascular Aging ◽  
Age Related ◽  
Arterial Aging ◽  
Artery Stiffness ◽  
Elastic Artery

Aging is the major risk factor for cardiovascular diseases (CVD). This is attributable primarily to adverse changes in arteries, notably, increases in large elastic artery stiffness and endothelial dysfunction mediated by inadequate concentrations of the vascular-protective molecule, nitric oxide (NO), and higher levels of oxidative stress and inflammation. Inorganic nitrite is a promising precursor molecule for augmenting circulating and tissue NO bioavailability because it requires only a one-step reduction to NO. Nitrite also acts as an independent signaling molecule, exerting many of the effects previously attributed to NO. Results of recent studies indicate that nitrite may be effective in the treatment of vascular aging. In old mice, short-term oral sodium nitrite supplementation reduces aortic pulse wave velocity, the gold-standard measure of large elastic artery stiffness, and ameliorates endothelial dysfunction, as indicated by normalization of NO-mediated endothelium-dependent dilation. These improvements in age-related vascular dysfunction with nitrite are mediated by reductions in oxidative stress and inflammation, and may be linked to increases in mitochondrial biogenesis and health. Increasing nitrite levels via dietary intake of nitrate appears to have similarly beneficial effects in many of the same physiological and clinical settings. Several clinical trials are being performed to determine the broad therapeutic potential of increasing nitrite bioavailability on human health and disease, including studies related to vascular aging. In summary, inorganic nitrite, as well as dietary nitrate supplementation, represents a promising therapy for treatment of arterial aging and prevention of age-associated CVD in humans.

scholarly journals Gender Differences in Large Artery Stiffness Pre- and Post Puberty

2003 ◽  
Vol 88 (11) ◽  
pp. 5375-5380 ◽  
Author(s):  
Anna A. Ahimastos ◽  
Melissa Formosa ◽  
Anthony M. Dart ◽  
Bronwyn A. Kingwell
Keyword(s):  
Gender Differences ◽  
Heart Rate ◽  
Cardiac Output ◽  
Arterial Compliance ◽  
Large Artery ◽  
Healthy Children ◽  
Large Arteries ◽  
Age Related ◽  
Artery Stiffness ◽  
Males And Females

Abstract Age-related large artery stiffening is more pronounced in women compared with men and is an important cause of isolated systolic hypertension. This study aimed to investigate whether such gender differences are inherent or the result of sex steroid influences. Healthy children prepuberty [26 female (10.3 ± 0.1 yr), 32 male (10.3 ± 0.1 yr), mean age ± sd] and post puberty [30 female (15.9 ± 0.2 yr), 22 male (15.9 ± 0.4 yr)] were studied. Large artery stiffness was assessed globally via systemic arterial compliance and regionally via pulse wave velocity. Prepubertal males and females did not differ in body size, cardiac output, or heart rate. Prepubertal females had stiffer large arteries and higher pulse pressure than age-matched males (P < 0.05). Postpubertal males were taller and heavier and had a greater cardiac output and lower heart rate compared with similarly aged females. In relation to pubertal status, females developed more distensible large arteries post puberty whereas males developed stiffer large vessels (P < 0.05). These changes where such that central large artery stiffness was similar between genders in the postpubertal group. Together these data suggest that large artery stiffness varies intrinsically between genders but is also modulated by both male and female sex steroids.

Assessment of the Vascular Effects of PC6 (Neiguan) Using the Second Derivative of the Finger Photoplethysmogram in Healthy and Hypertensive Subjects

2007 ◽  
Vol 35 (03) ◽  
pp. 427-436 ◽  
Author(s):  
José F. Rivas-Vilchis ◽  
Fernando Hernández-Sánchez ◽  
Ramón González-Camarena ◽  
Luis D. Suárez-Rodríguez ◽  
Ricardo Escorcia-Gaona ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Light Transmission ◽  
Infrared Light ◽  
Second Derivative ◽  
Large Artery ◽  
Vascular Aging ◽  
Acute Effects ◽  
Vascular Effects ◽  
Artery Stiffness ◽  
Volume Pulse

Indices obtained from the second derivative of the digital volume pulse waveform have been proposed to characterize vascular aging, arterial rigidity, and the effects of vasoactive drugs. The purpose of this study was to assess the effects of manual needling of PC6 on SDDVP indices in healthy and untreated hypertensive subjects. AI, B:A, and D:A indices, based on the height of the wave components of SDDVP, in 40 healthy subjects and 25 untreated hypertensive subjects were compared. DVP was obtained by measuring infrared light transmission through the finger. For each subject, 20-min-long DVP registration was obtained. PC6 was stimulated unilaterally by manual needling for 5 min (1–6 min). In each subject, pre-acupuncture DVP indices were compared to those of during acupuncture (1 vs. 4 min) and post-acupuncture (1 vs. 18 min). In healthy subjects, AI was significantly improved when comparing the pre- to the post-acupuncture values. In hypertensive subjects, the SDDVP indices improved significantly as follows: the AI index when the value of pre-acupuncture comparing to that of during acupuncture and post-acupuncture values; B:A and D:A indices when the pre-comparing to post-acupuncture values. There were significant differences between healthy and hypertensive subjects in AI, B:A, and D:A at baseline and in B:A in the during acupuncture period; there were no significant differences at post-acupuncture. These results indicate that manual needling of PC6 produced acute effects on vascular pathophysiology. Moreover, PC6 needling produced changes in SDDVP indices related to both large artery stiffness and the reflected wave originating in small arteries.

scholarly journals Sirtuin 1 in Endothelial Dysfunction and Cardiovascular Aging

2021 ◽  
Vol 12 ◽  
Author(s):  
Stefano Ministrini ◽  
Yustina M. Puspitasari ◽  
Georgia Beer ◽  
Luca Liberale ◽  
Fabrizio Montecucco ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Animal Models ◽  
Nicotinamide Adenine Dinucleotide ◽  
Sirtuin 1 ◽  
Future Research ◽  
Metabolic Functions ◽  
Potential Mediator ◽  
Age Related ◽  
The Family

Sirtuin 1 (SIRT1) is a histone deacetylase belonging to the family of Sirtuins, a class of nicotinamide adenine dinucleotide (NAD+)-dependent enzymes with multiple metabolic functions. SIRT1 localizes in the nucleus and cytoplasm, and is implicated in the regulation of cell survival in response to several stimuli, including metabolic ones. The expression of SIRT1 is associated with lifespan and is reduced with aging both in animal models and in humans, where the lack of SIRT1 is regarded as a potential mediator of age-related cardiovascular diseases. In this review, we will summarize the extensive evidence linking SIRT1 functional and quantitative defects to cellular senescence and aging, with particular regard to their role in determining endothelial dysfunction and consequent cardiovascular diseases. Ultimately, we outline the translational perspectives for this topic, in order to highlight the missing evidence and the future research steps.

Oxidative stress and inflammation are associated with age-related endothelial dysfunction in men with low testosterone

2021 ◽  
Author(s):  
Matthew C Babcock ◽  
Lyndsey E DuBose ◽  
Teresa L Witten ◽  
Brian L Stauffer ◽  
Kerry L Hildreth ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Vitamin C ◽  
Density Lipoprotein ◽  
Saline Control ◽  
Vascular Aging ◽  
Cvd Risk ◽  
Cross Sectional ◽  
Age Related ◽  
Low Testosterone

Abstract Context Vascular aging, including endothelial dysfunction secondary to oxidative stress and inflammation, increases the risk for age-associated cardiovascular disease (CVD). Low testosterone in middle-age and older (MA/O) men is associated with increased CVD risk. Objectives We hypothesized that low testosterone contributes to age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. Design Cross-sectional. Participants Fifty-eight healthy, non-smoking men categorized as young (N=20; age: 29±4 years, testosterone: 500±58 ng/dL), MA/O with higher testosterone (N=20; age: 60±6 years, testosterone: 512±115 ng/dL), and MA/O lower testosterone (N=18; age 59±8 years, testosterone: 269±48 ng/dL). Main Outcome Measures Brachial artery flow-mediated dilation (FMDBA) measured during acute infusion of saline (control) and vitamin C (antioxidant). Markers of oxidative stress (total antioxidant status [TAS] and oxidized low-density lipoprotein [LDL] cholesterol), inflammation (interleukin [IL]-6 and C-reactive protein [CRP]), and androgen deficiency symptoms were also examined. RESULTS: During saline, FMDBA was reduced in MA/O compared to young, regardless of testosterone status (P<0.001). FMDBA was reduced in MA/O lower testosterone (3.7±2.0%) compared to MA/O higher testosterone (5.7±2.2%, p=0.021), independent of symptoms. Vitamin C increased FMDBA (to 5.3±1.6%, p=0.022) in MA/O lower testosterone but had no effect in young (P=0.992) or MA/O higher testosterone (P=0.250). FMDBA correlated with serum testosterone (r=0.45, p<0.001), IL-6 (r=-0.41, P=0.002), and CRP (r=-0.28, P=0.041). Conclusions Healthy MA/O men with low testosterone appear to have greater age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. These data suggest that low testosterone concentrations may contribute to accelerated vascular aging in men.

Determination of age-related increases in large artery stiffness by digital pulse contour analysis

2002 ◽  
Vol 103 (4) ◽  
pp. 371-377 ◽  
Author(s):  
S.C. MILLASSEAU ◽  
R.P. KELLY ◽  
J.M. RITTER ◽  
P.J. CHOWIENCZYK
Keyword(s):  
Glyceryl Trinitrate ◽  
Pulse Contour Analysis ◽  
Pulse Contour ◽  
Applanation Tonometry ◽  
Large Artery ◽  
Contour Analysis ◽  
Arterial Blood ◽  
Age Related ◽  
Digital Pulse ◽  
Artery Stiffness

The stiffness of the aorta can be determined by measuring carotid–femoral pulse wave velocity (PWVcf). PWV may also influence the contour of the peripheral pulse, suggesting that contour analysis might be used to assess large artery stiffness. An index of large artery stiffness (SIDVP) derived from the digital volume pulse (DVP) measured by transmission of IR light (photoplethysmography) was examined. SIDVP was obtained from subject height and from the time delay between direct and reflected waves in the DVP. The timing of these components of the DVP is determined by PWV in the aorta and large arteries. SIDVP was, therefore, expected to provide a measure of stiffness similar to PWV. SIDVP was compared with PWVcf obtained by applanation tonometry in 87 asymptomatic subjects (21–68 years; 29 women). The reproducibility of SIDVP and PWVcf and the response of SIDVP to glyceryl trinitrate were assessed in subsets of subjects. The mean within-subject coefficient of variation of SIDVP, for measurements at weekly intervals, was 9.6%. SIDVP was correlated with PWVcf (r = 0.65, P<0.0001). SIDVP and PWVcf were each independently correlated with age and mean arterial blood pressure (MAP) with similar regression coefficients: SIDVP = 0.63+0.086×age+0.042×MAP (r = 0.69, P<0.0001); PWVcf = 0.76+0.080×age+0.053×MAP (r = 0.71, P<0.0001). Administration of glyceryl trinitrate (3, 30 and 300 μg/min intravenous; each dose for 15 min) in nine healthy men produced similar changes in SIDVP and PWVcf. Thus contour analysis of the DVP provides a simple, reproducible, non-invasive measure of large artery stiffness.

Vascular and Endothelial Biology of Aging

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. SCI-5-SCI-5
Author(s):  
Frank M. Faraci
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Transgenic Mice ◽  
Nadph Oxidase ◽  
Endothelial Function ◽  
Vascular Dysfunction ◽  
Rho Kinase ◽  
Vascular Aging ◽  
Age Related ◽  
The Brain

Abstract Although aging is one of the greatest risk factors for vascular disease, very little is known regarding mechanisms that control the progression of vascular aging at the level of the endothelial cell. Endothelial dysfunction - a critical element of carotid artery and cerebrovascular disease - progresses with age, contributing to hypoperfusion, increased risk for ischemic stroke, and cognitive decline. Studies from several laboratories support the concept that age-induced endothelial dysfunction may occur earlier and be larger in magnitude in the cerebral circulation than in blood vessels outside of the brain. Thus, the circulationof the brain may be particularly sensitive to age-induced endothelial dysfunction. In relation to underlying mechanisms, angiotensin II type 1 receptors, NADPH oxidase, and oxidative stress appear to play a key role in age-related vascular dysfunction. The nuclear receptor peroxisome proliferator-activated receptor-g (PPARg) exerts protective effects in the vasculature when pharmacologically activated. We recently examined the hypothesis that endothelial PPARg protects against vascular aging. We studied carotid arteries from adult and old transgenic mice with endothelial specific expression of a human dominant negative mutation in PPARg driven by the vascular cadherin promoter (designated E-V290M), along with non-transgenic littermates. Endothelial function was similar in arteries from adult non-transgenic and E-V290M mice as well as old non-transgenic mice. In contrast, there was a marked reduction in endothelial function in old E-V290M mice. This augmented endothelial dysfunction was not altered by inhibition of cyclooxygenase, but was restored to normal by a superoxide scavenger, an inhibitor of NADPH oxidase, or inhibition of Rho kinase. Oxidant and inflammatory related mechanisms often interact. Vascular expression of interleukin-6, another mediator of vascular disease, was increased 1.6-fold in old non-transgenic mice, but almost 9-fold in old E-V290M mice. Expression of CDKN2A, a molecular marker of senescence, was ~two-fold greater in old E-V290M mice compared to controls. These findings provide the first evidence that senescence and age-related vascular dysfunction is accelerated following cell-specific interference with endothelial PPARg through mechanisms that involve oxidative stress, inflammation, and Rho kinase. This critical role for endothelial PPARg has implications for vascular pathophysiology as well as therapeutic approaches for age-induced large and small vessel disease. Disclosures No relevant conflicts of interest to declare.

scholarly journals Elevated plasma homocysteine and cysteine are associated with endothelial dysfunction across menopausal stages in healthy women

2019 ◽  
Vol 126 (6) ◽  
pp. 1533-1540 ◽  
Author(s):  
Amy C. Keller ◽  
Jelena Klawitter ◽  
Kerry L. Hildreth ◽  
Uwe Christians ◽  
Kelly Putnam ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Dietary Intake ◽  
Postmenopausal Women ◽  
Plasma Concentrations ◽  
Flow Mediated Dilation ◽  
Future Studies ◽  
Healthy Women ◽  
Menopause Transition ◽  
Artery Flow ◽  
Estradiol Levels

Hyperhomocysteinemia is associated with endothelial dysfunction and increased cardiovascular disease (CVD). We determined whether elevated homocysteine (Hcy) and markers of Hcy metabolism were associated with the previously reported endothelial dysfunction across stages of the menopause transition. Brachial artery flow-mediated dilation (FMD) and plasma concentrations of Hcy, cysteine, and methionine were measured in healthy women ( n = 128) 22–70 yr of age categorized as premenopausal ( n = 35), perimenopausal (early: n = 16; late: n = 21), and postmenopausal (early: n = 21; late: n = 35). Dietary intake of micronutrients involved in Hcy metabolism (e.g., vitamins B6, B12, folate) was assessed in a subpopulation of women. Hcy and cysteine concentrations were progressively higher, and methionine was progressively lower across menopausal stages (all P < 0.005). The higher Hcy and cysteine concentrations correlated with lower circulating estradiol levels ( r = −0.49 and −0.50, respectively, both P < 0.001). FMD was inversely correlated with Hcy ( r = −0.25, P = 0.004) and cysteine ( r = −0.39, P < 0.001) and positively correlated with methionine concentrations ( r = 0.25, P = 0.005). Dietary intake of vitamins B6 and B12 (both P < 0.05) were lower in postmenopausal women. Vitamin B12 intake correlated with FMD ( r = 0.22, P = 0.006). These data suggest that declines in estradiol across stages of the menopause transition may lead to elevations in Hcy and cysteine that may contribute to endothelial dysfunction in postmenopausal women. Future studies should examine whether targeting Hcy metabolism during the perimenopausal to early postmenopausal period with interventions, including diet, attenuates or reverses the decline in endothelial function in women.NEW & NOTEWORTHY Declines in circulating estradiol across the stages of the menopausal transition may lead to elevations in Hcy and cysteine concentrations that may contribute to endothelial dysfunction. Abnormalities in the Hcy metabolic pathways, possibly related to dietary deficiencies of vitamins B12 and B6 and folate, may contribute to elevations in Hcy and cysteine concentrations. Findings also suggest that higher cysteine levels may be more damaging to the vascular endothelium than Hcy.

scholarly journals Large Artery Stiffness and Brain Health: Insights from Animal Models

2020 ◽  
Author(s):  
Nicholas R Winder ◽  
Emily H Reeve ◽  
Ashley E Walker
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Brain Aging ◽  
Large Artery ◽  
Neurocognitive Dysfunction ◽  
Disease Etiology ◽  
Age Related ◽  
Artery Stiffness ◽  
Underlying Mechanisms

There are no effective treatments available to halt or reverse the progression of age-related cognitive decline and Alzheimer's disease. Thus, there is an urgent need to understand the underlying mechanisms of disease etiology and progression in order to identify novel therapeutic targets. Age-related changes to vasculature, particularly increases in stiffness of the large elastic arteries, are now recognized as important contributors to brain aging. There is a growing body of evidence for an association between greater large artery stiffness and cognitive impairment among both healthy older adults and patients with Alzheimer's disease. However, studies in humans are limited to only correlative evidence while animal models allow researchers to explore the causative mechanisms linking arterial stiffness to neurocognitive dysfunction and disease. Recently, several rodent models of direct modulation of large artery stiffness and the consequent effects on the brain have been reported. Common outcomes among these models have emerged, including evidence that greater large artery stiffness causes cerebrovascular dysfunction associated with increased oxidative stress and inflammatory signaling. The purpose of this mini review is to highlight recent findings associating large artery stiffness with deleterious brain outcomes, with a specific focus on causative evidence obtained from animal models. We will also discuss the gaps in knowledge that remain in our understanding of how large artery stiffness affects brain function and disease outcomes.

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