Alterations In Vascular Function Research Articles

Early remodeling and loss of light-induced dilation of retinal small arteries in CADASIL

A major hurdle to therapeutic development in cerebral small vessel diseases is the lack of in-vivo method that can be used repeatedly for evaluating directly cerebral microvessels. We hypothesised that Adaptive Optics (AO), which allows resolution images up to 1–2 μm/pixel at retinal level, could provide a biomarker for monitoring vascular changes in CADASIL, a genetic form of such condition. In 98 patients and 35 healthy individuals, the wall to lumen ratio (WLR), outer and inner diameter, wall thickness and wall cross-sectional area were measured in a parapapillary and/or paramacular retinal artery. The ratio of vessel diameters before and after light flicker stimulations was also calculated to measure vasoreactivity (VR). Multivariate mixed-model analysis showed that WLR was increased and associated with a larger wall thickness and smaller internal diameter of retinal arteries in patients. The difference was maximal at the youngest age and gradually reduced with aging. Average VR in patients was less than half of that of controls since the youngest age. Any robust association was found with clinical or imaging manifestations of the disease. Thus, AO enables the detection of early functional or structural vascular alterations in CADASIL but with no obvious link to the clinical or imaging severity.

Linking Malaria and Hypertension: Unveiling the Interconnected Pathophysiological Nexus

Malaria, a devastating infectious disease caused by Plasmodium parasites, has long been recognized for its direct impact on global health. Recent studies have unveiled a potential connection between malaria infection and the development of hypertension, a prevalent cardiovascular disorder worldwide. Understanding the underlying pathophysiological mechanisms linking these seemingly disparate conditions is crucial for comprehensive disease management and prevention. The pathogenesis of malaria involves complex interactions between the parasite and the host immune system, resulting in systemic inflammation, endothelial dysfunction, and organ damage. Chronic exposure to Plasmodium infection induces alterations in vascular function, hemodynamics, and immune responses, potentially contributing to the development of hypertension. Several proposed mechanisms underscore the link between malaria and hypertension, including chronic inflammation, oxidative stress, endothelial dysfunction, and dysregulation of the renin-angiotensin-aldosterone system (RAAS). These mechanisms intertwine to disturb vascular homeostasis, leading to increased peripheral resistance and elevated blood pressure. Furthermore, the longterm consequences of repeated malaria episodes, especially in endemic regions, may potentiate vascular remodeling and contribute to the onset or exacerbation of hypertension in affected individuals. Genetic predispositions and environmental factors also play pivotal roles in modulating susceptibility to both malaria and hypertension. Recognition of this intricate association between malaria and hypertension prompts the necessity for integrated healthcare approaches encompassing effective malaria control strategies, early detection, and management of hypertension in endemic regions. Targeted interventions addressing common pathways, such as inflammation and endothelial dysfunction, may offer potential therapeutic avenues. Keywords: Malaria, Hypertension, Pathophysiology, Inflammation, Endothelial Dysfunction, Plasmodium Parasites, Cardiovascular Disorders, Immune Response, Vascular Remodeling, Global Health.

ASSOCIATION OF BIOCHEMICAL, CLINICAL, AND ANTHROPOMETRIC PARAMETERS WITH FUNCTIONAL PERFORMANCE OF OLDER WOMEN

Abstract Increased longevity is a widespread worldwide trend, evidenced by demographic and epidemiological data, especially with regard to females, who live an average of seven years longer than males. The aging process is associated with a progressive decline in muscle mass, strength, power, impaired balance, altered heart function and vascular function. These changes negatively affect exercise capacity, increase the risk of cardiovascular disease, and have implications for physical function and the risk of falling. This is particularly relevant among women diagnosed with impaired functional performance. The aim of this study was to determine an association of biochemical, anthropometric, metabolic and inflammatory parameters according to the functional performance of older women aged 62 to 75 years attended for in primary health care. Statistical results showed that the 116 older women (56.86%) identified with impaired functional performance had a pro-inflammatory marker, high anthropometric indices and body composition, impaired cognitive performance and lower muscle strength as older women ( 88 ) with normal functional performance (43.14%). Age, waist-to-height ratio and elevated IL-6 and muscle strength significantly decreased the risk of impaired functional performance. These important findings demonstrate the need for further research documenting the underlying processes and risk factors for preserving functional capacity, carrying out life activities and decreasing the emergence of illnesses. The potential benefits of this approach provide a basis for developing individualized health promotion interventions in the management of this population of older women.

Modulating NO-GC Pathway in Pulmonary Arterial Hypertension.

The pathogenesis of complex diseases such as pulmonary arterial hypertension (PAH) is entirely rooted in changes in the expression of some vasoactive factors. These play a significant role in the onset and progression of the disease. Indeed, PAH has been associated with pathophysiologic alterations in vascular function. These are often dictated by increased oxidative stress and impaired modulation of the nitric oxide (NO) pathway. NO reduces the uncontrolled proliferation of vascular smooth muscle cells that leads to occlusion of vessels and an increase in pulmonary vascular resistances, which is the mainstay of PAH development. To date, two classes of NO-pathway modulating drugs are approved for the treatment of PAH: the phosphodiesterase-5 inhibitors (PD5i), sildenafil and tadalafil, and the soluble guanylate cyclase activator (sGC), riociguat. Both drugs provide considerable improvement in exercise capacity and pulmonary hemodynamics. PD5i are the recommended drugs for first-line PAH treatment, whereas sGCs are also the only drug approved for the treatment of resistant or inoperable chronic thromboembolic pulmonary hypertension. In this review, we will focus on the current information regarding the nitric oxide pathway and its modulation in PAH.

Vascular determinants of hippocampal viscoelastic properties in healthy adults across the lifespan

Arterial stiffness and cerebrovascular pulsatility are non-traditional risk factors of Alzheimer’s disease. However, there is a gap in understanding the earliest mechanisms that link these vascular determinants to brain aging. Changes to mechanical tissue properties of the hippocampus (HC), a brain structure essential for memory encoding, may reflect the impact of vascular dysfunction on brain aging. We tested the hypothesis that arterial stiffness and cerebrovascular pulsatility are related to HC tissue properties in healthy adults across the lifespan. Twenty-five adults underwent measurements of brachial blood pressure (BP), large elastic artery stiffness, middle cerebral artery pulsatility index (MCAv PI), and magnetic resonance elastography (MRE), a sensitive measure of HC viscoelasticity. Individuals with higher carotid pulse pressure (PP) exhibited lower HC stiffness (β = −0.39, r = −0.41, p = 0.05), independent of age and sex. Collectively, carotid PP and MCAv PI significantly explained a large portion of the total variance in HC stiffness (adjusted R2 = 0.41, p = 0.005) in the absence of associations with HC volumes. These cross-sectional findings suggest that the earliest reductions in HC tissue properties are associated with alterations in vascular function.

Clinical Significance of Altered Vascular Morphology and Function in Normotension.

To review current literature examining the presence of subclinical micro- and macrovascular alterations in normotensive individuals and their clinical significance in terms of hypertension prediction. Emphasis is placed on alterations that can be detected in peripheral vascular beds using non-invasive, easily applicable methodology, as these are in general easier to capture and evaluate in clinical practice compared to more complex invasive or functional tests. Arterial stiffness, increased carotid intima-media thickness, and altered retinal microvascular diameters predict the progression from the normotensive to the hypertensive state. By contrast, there is substantial lack of relevant prospective studies for skin microvascular alterations. Although conclusions regarding causality cannot be safely deduced from available studies, detection of morphological and functional vascular alterations in normotensive individuals emerges as a sensitive indicator of progression to hypertension and hence increased CVD risk. An increasing amount of evidence suggests that early detection of subclinical micro- and macrovascular alterations would be clinically useful for the early identification of individuals at high risk for future hypertension onset. Methodological issues and gaps in knowledge need to be addressed before detection of such changes could guide the development of strategies to prevent new-onset hypertension in normotensive individuals.

Interaction of Biochemical Processes between Chronic Obstructive Pulmonary Disease (COPD), Pulmonary Arterial Hypertension (PAH), and Coronavirus Disease 2019 (COVID-19).

Both pulmonary arterial hypertension (PAH) and chronic obstructive pulmonary disease (COPD) are risk factors for coronavirus disease 2019 (COVID-19). Patients with lung injury and altered pulmonary vascular anatomy or function are more susceptible to infections. The purpose of the study is to ascertain whether individuals with COPD or PAH are affected synergistically by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data sources for the construction of a protein-protein interaction (PPI) network and the identification of differentially expressed genes (DEGs) included three RNA-seq datasets from the GEO database (GSE147507, GSE106986, and GSE15197). Then, relationships between miRNAs, common DEGs, and transcription factor (TF) genes were discovered. Functional analysis using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and other databases, as well as the forecasting of antiviral medications for COPD and PAH patients infected with SARS-CoV-2, were also performed. Eleven common DEGs were found in the three datasets, and their biological functions were primarily enriched in the control of protein modification processes, particularly phosphorylation. Growth factor receptor binding reflects molecular function. KEGG analysis indicated that co-DEGs mainly activate Ras, and PI3K-Akt signaling pathways and act on focal adhesions. NFKB1 interacted with HSA-miR-942 in the TF-miRNA-DEGs synergistic regulatory network. Acetaminophen is considered an effective drug candidate. There are some connections between COPD and PAH and the development of COVID-19. This research could aid in developing COVID-19 vaccines and medication candidates that would work well as COVID-19 therapies.

Ultrafast Doppler imaging and ultrasound localization microscopy reveal the complexity of vascular rearrangement in chronic spinal lesion

Acute spinal cord injury (SCI) leads to severe damage to the microvascular network. The process of spontaneous repair is accompanied by formation of new blood vessels; their functionality, however, presumably very important for functional recovery, has never been clearly established, as most studies so far used fixed tissues. Here, combining ultrafast Doppler imaging and ultrasound localization microscopy (ULM) on the same animals, we proceeded at a detailed analysis of structural and functional vascular alterations associated with the establishment of chronic SCI, both at macroscopic and microscopic scales. Using a standardized animal model of SCI, our results demonstrate striking hemodynamic alterations in several subparts of the spinal cord: a reduced blood velocity in the lesion site, and an asymmetrical hypoperfusion caudal but not rostral to the lesion. In addition, the worsening of many evaluated parameters at later time points suggests that the neoformed vascular network is not yet fully operational, and reveals ULM as an efficient in vivo readout for spinal cord vascular alterations. Finally, we show statistical correlations between the diverse biomarkers of vascular dysfunction and SCI severity. The imaging modality developed here will allow evaluating recovery of vascular function over time in pre-clinical models of SCI. Also, used on SCI patients in combination with other quantitative markers of neural tissue damage, it may help classifying lesion severity and predict possible treatment outcomes in patients.

Altered cardiac and vascular stiffness in pregnancy after a hypertensive pregnancy

Hypertensive disorders of pregnancy are an important cause of morbidity and mortality, impacting on both maternal and fetal wellbeing. Affected women are at higher risk of future cardiovascular morbidity and mortality. Our study objective was to assess differences in cardiovascular function in pregnant women previously affected by gestational hypertension or preeclampsia. Pregnant women diagnosed with gestational hypertension or preeclampsia in a previous pregnancy were recruited at the start of a subsequent pregnancy and compared to healthy pregnant and non-pregnant controls. All patients underwent pulse wave analysis and echocardiography. Indexes of echocardiography-derived arterial and left ventricular elastance were calculated. In our study women with prior hypertension (n = 25) were more likely to have blood pressure in the 120–139/80–99 mmHg (prehypertension) range. Women with previous hypertension in pregnancy had increased late diastolic transmitral flow velocities (A wave) and increased augmentation index. Women without prior hypertension (n = 50) demonstrated more compliance (reduced EaI and Ees) compared to the non-pregnant controls (n = 40). This adaptation was not seen in pregnancy with prior hypertension, where increased arterial stiffness was observed. In conclusion we have shown increased prevalence of prehypertension and increased arterial stiffness in pregnant women previously affected by gestational hypertensive disease. An increased atrial component to ventricular filling reflects altered diastolic function after hypertensive pregnancy. These women are at increased future cardiovascular risk due to altered cardiac and vascular function and require effective risk mitigation.

Impact of maternal diabetes exposure on soluble adhesion molecules in the offspring

Background and aimsSoluble adhesion molecules are associated with cardiovascular disease and increased in individuals with diabetes. This study assesses the impact of diabetes exposure in utero on the abundance of circulating adhesion molecules in cord serum and soluble adhesion molecules released from human umbilical vein endothelial cells (HUVEC) exposed to high glucose concentrations. Methods and resultsWomen with and without diabetes were recruited. DM was diagnosed based on the American Diabetes Association criteria. Primary cultures of HUVEC were cultured in 5 mM and 25 mM glucose with 25 mM mannitol osmotic control. The soluble adhesion molecules, intracellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) and E-selectin were measured by ELISA in the cord blood serum and conditioned HUVEC media. The mothers with DM were older with higher BMI (p = 0.027 and 0.008, respectively). In a fully adjusted model, VCAM was significantly increased in the cord serum of infants born to mothers with diabetes (p = 0.046), but ICAM and E-selectin were not different. ICAM was also significantly correlated with maternal HbA1c (r2 = 0.16, p = 0.004) and cord serum non-esterified fatty acids (r2 = 0.08, p = 0.013). From the HUVEC media, the abundance of adhesion molecules was not different based on DM or high glucose exposure; however, VCAM abundance in the HUVEC supernatant was significantly correlated with ICAM (r2 = 0.27, p = 0.010) and cord serum c-peptide (R2 = 0.19, p = 0.043). ConclusionsAlterations in soluble adhesion molecule abundance in infants exposed to the diabetic milieu of pregnancy may reflect early alterations in vascular function predicting future cardiovascular disease.

Vasoconstrictor antagonism improves functional and structural vascular alterations and liver damage in rats with early NAFLD

Background & AimsIntrahepatic vascular resistance is increased in early non-alcoholic fatty liver disease (NAFLD), potentially leading to tissue hypoxia and triggering disease progression. Hepatic vascular hyperreactivity to vasoconstrictors has been identified as an underlying mechanism. This study investigates vasoconstrictive agonism and antagonism in 2 models of early NAFLD and in non-alcoholic steatohepatitis (NASH).MethodsThe effects of endothelin-1 (ET-1), angiotensin II (ATII) and thromboxane A2 (TxA2) agonism and antagonism were studied by in situ ex vivo liver perfusion and preventive/therapeutic treatment experiments in a methionine-choline-deficient diet model of steatosis. Furthermore, important results were validated in Zucker fatty rats after 4 or 8 weeks of high-fat high-fructose diet feeding. In vivo systemic and portal pressures, ex vivo transhepatic pressure gradients (THPG) and transaminase levels were measured. Liver tissue was harvested for structural and mRNA analysis.ResultsThe THPG and consequent portal pressure were significantly increased in both models of steatosis and in NASH. ET-1, ATII and TxA2 increased the THPG even further. Bosentan (ET-1 receptor antagonist), valsartan (ATII receptor blocker) and celecoxib (COX-2 inhibitor) attenuated or even normalised the increased THPG in steatosis. Simultaneously, bosentan and valsartan treatment improved transaminase levels. Moreover, bosentan was able to mitigate the degree of steatosis and restored the disrupted microvascular structure. Finally, beneficial vascular effects of bosentan endured in NASH.ConclusionsAntagonism of vasoconstrictive mediators improves intrahepatic vascular function. Both ET-1 and ATII antagonists showed additional benefit and bosentan even mitigated steatosis and structural liver damage. In conclusion, vasoconstrictive antagonism is a potentially promising therapeutic option for the treatment of early NAFLD.Lay summaryIn non-alcoholic fatty liver disease (NAFLD), hepatic blood flow is impaired and the blood pressure in the liver blood vessels is increased as a result of an increased response of the liver vasculature to vasoconstrictors. Using drugs to block the constriction of the intrahepatic vasculature, the resistance of the liver blood vessels decreases and the increased portal pressure is reduced. Moreover, blocking the vasoconstrictive endothelin-1 pathway restored parenchymal architecture and reduced disease severity.

Non-Invasive Detection of Fetal Vascular Endothelial Function in Gestational Diabetes Mellitus.

ObjectivesEndothelial dysfunction in the fetuses of women with gestational diabetes mellitus (GDM) is associated with their subsequent cardiovascular events. Prenatal assessment of endothelial function in fetuses exposed to intrauterine hyperglycemic environment remains challenging. The aim of this study was to assess the fetal vascular endothelial function in GDM patients using color M-mode derived aortic propagation velocity (APV) and evaluate the correlation of APV with endothelial function biomarkers.MethodsThis observational cross-sectional study included 31 gestational diabetic mothers and 30 healthy pregnant mothers from August 2019 to January 2020. Clinical data were compared between the groups. Fetal APV was measured using color M-mode echocardiography at late gestation. Concentrations of endothelial biomarkers including von Willebrand Factor (vWF), vascular endothelial-cadherin and endothelin-1 in umbilical cord serum were assessed. Measurements between diabetic group and controls were compared.ResultsvWF was the only endothelial functional marker that differed between the two groups. Fetuses in the GDM group had significantly lower APV levels and higher vWF levels compared with the healthy controls (P < 0.05). There was a moderate but significant correlation between APV and vWF (r =−0.58, P < 0.001). There were no associations between APV and ventricular wall thickness or umbilical artery pulsatility index.ConclusionsColor M-mode propagation velocity of aorta is a non-invasive, practical method that correlates well with GDM and fetal endothelial function. This novel metric could contribute to recognizing early vascular functional alterations and hence represents a potential strategy for early risk factor surveillance and risk modification.

P105 Endocrine, autonomic and vascular function in children with Sleep Disordered Breathing

Abstract SDB is a risk factor for cardiovascular disease and co-exists with chronic endocrine disorders such as type II diabetes and metabolic syndrome. Children with SDB have increased blood flow velocity, an indicator of reduced vascular compliance and early vascular aging. Increased blood flow velocity is positively associated with sympathetic activity, increased arterial sympathetic nerve fibre density and endothelial damage. Whether changes in endocrine function occur concomitantly with altered autonomic and vascular function in children with SDB was assessed. Thirty six children scheduled for tonsillectomy underwent overnight polysomnography (SDB severity), pupil light reflex (autonomic function), fasting brachial artery blood flow assessment (vascular function - Doppler Ultrasound). Leptin and Ghrelin - both hormonal markers associated with sympathetic activity were measured in urine using ELISA and serum using MagPlex. The following dimensions of the dorsal lingual artery (tonsil) were measured – medial thickness, medial area, smooth muscle cell number/layers. We observed a positive correlation between serum and urine leptin and ghrelin concentrations. Increased blood flow velocity and arterial medial thickness were both associated with increased serum and urine leptin and ghrelin concentrations. Pupil light reflex was negatively associated with serum leptin and ghrelin levels. OAHI was positively correlated with leptin and ghrelin concentration (urine and serum) but not blood flow velocity. Blood flow velocity was inversely correlated with SpO2 nadir (REM). Our findings suggest that SDB has a global effect on the autonomic, vascular and endocrine systems.The impact of untreated paediatric SDB on the development of comorbidities in later life needs urgent attention.

The Neurovascular Unit in Dementia: An Opinion on Current Research and Future Directions.

Dementia is a burgeoning public health crisis, with 50 million people currently affected worldwide (Prince et al., 2015). As the population ages, this figure is set to rise dramatically by 40% over the next 12 years (Prince et al., 2015). Dementia is an umbrella term for several disorders which result in the progressive loss of memory or other cognitive functions (Scott and Barrett, 2007). It remains an incurable disease, and current therapeutics have limited efficacy at slowing disease progression for one third of patients (Rockwood et al., 2008). Of the dementia sub-types, Alzheimer's disease (AD) remains the most prevalent, accounting for ~60–70% cases (Alzheimer's-Society, 2016). Vascular dementia (VaD) is the second most common form and is responsible for ~20% of cases, with a further 10% being a combination of these two diseases (Alzheimer's-Society, 2016). However, in practise these distinctions are somewhat arbitrary given the significant overlap in altered vascular structure and function in both of these major sub-types (Kalaria and Ballard, 1999). At least 30% of patients with AD have evidence of cerebrovascular disease on post-mortem examination, and almost all have evidence of cerebral amyloid angiopathy, microvascular degeneration, and white matter lesions (Kalaria and Ballard, 1999). Similarly, one-third of patients with VaD exhibit pathology consistent with AD (e.g., hippocampal or temporal lobe atrophy) (Kalaria and Ballard, 1999). Longitudinal studies have demonstrated that vascular risk factors (e.g., hypertension), significantly increase the risk of both AD and VaD (Rius-Perez et al., 2018). In genetically at-risk individuals positive for apolipoprotein E4 (APOE4), atherosclerosis can increase the risk of AD by three-fold (Hoffmann et al., 2010). This article provides an opinion on the current evidence on the role of the neurovascular unit in dementia, for further information, several recent reviews are available on this topic (Nelson et al., 2016; Kisler et al., 2017).

Addition of Olive Leaf Extract to a Mixture of Algae and Extra Virgin Olive Oils Decreases Fatty Acid Oxidation and Synergically Attenuates Age-Induced Hypertension, Sarcopenia and Insulin Resistance in Rats.

Olive-derived products, such as virgin olive oil (EVOO) and/or olive leaf extracts (OLE), exert anti-inflammatory, insulin-sensitizing and antihypertensive properties and may be useful for stabilizing omega 3 fatty acids (n-3 PUFA) due to their high content in antioxidant compounds. In this study, the addition of OLE 4:0.15 (w/w) to a mixture of algae oil (AO) rich in n-3 PUFA and EVOO (25:75, w/w) prevents peroxides formation after 12 months of storage at 30 °C. Furthermore, the treatment with the oil mixture (2.5 mL/Kg) and OLE (100 mg/Kg) to 24 month old Wistar rats for 21 days improved the lipid profile, increased the HOMA-IR and decreased the serum levels of miRNAs 21 and 146a. Treatment with this new nutraceutical also prevented age-induced insulin resistance in the liver, gastrocnemius and visceral adipose tissue by decreasing the mRNA levels of inflammatory and oxidative stress markers. Oil mixture + OLE also attenuated the age-induced alterations in vascular function and prevented muscle loss by decreasing the expression of sarcopenia-related markers. In conclusion, treatment with a new nutraceutical based on a mixture of EVOO, AO and OLE is a useful strategy for improving the stability of n-3 PUFA in the final product and to attenuate the cardiometabolic and muscular disorders associated with aging.

154-LB: Impact of Maternal Diabetes Exposure on Soluble Adhesion Molecules

Soluble adhesion molecules are associated with cardiovascular disease and increased in individuals with diabetes. The current study assesses the impact of diabetes exposure in utero on the abundance of circulating adhesion molecules in cord serum as well as soluble adhesion molecules released from human umbilical vein endothelial cells (HUVEC) upon exposure to high levels of glucose. Women with and without diabetes (DM; gestational or type 2) were recruited at delivery. DM was diagnosed based on the criteria by the American Diabetes Association. Primary cultures of HUVEC were established in M199 medium with growth supplements. For the high glucose treatment, medium was adjusted to a final glucose concentration of 25mM with media collected 48 hours post treatment. The soluble adhesion molecules intracellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) and E-selectin were measured by ELISA in the cord blood serum and the conditioned HUVEC media. Serum adhesion molecules were measured in 42 infants born to mothers with normal glycemia and 35 infants of mothers with DM. The mothers with DM were older with higher BMI (p=0.027 and 0.008, respectively). In a fully adjusted model, VCAM was significantly increased in the cord serum of infants born to mothers with diabetes (p=0.046), but ICAM and E-selectin were not different. ICAM was significantly correlated with E-selectin (r2=0.25, p&amp;lt;0.001), but not VCAM. ICAM was also significantly correlated with maternal HbA1c (r2=0.16, p=0.004) and cord serum non-esterified fatty acids (r2=0.08, p=0.013). From the HUVEC, the abundance of adhesion molecules was not different based on DM or high glucose exposure; however, VCAM abundance in the HUVEC supernatant was significantly correlated with ICAM (r2=0.27, p=0.010) and cord serum insulin (r2=0.19, p=0.042). Alterations in soluble adhesion molecule abundance in infants exposed to the diabetic milieu of pregnancy may reflect early alterations in vascular function predicting future cardiovascular disease. Disclosure S. B. Landreth: None. A. M. Teague: None. M. Jensen: None. S. Gulati: None. J. B. Tryggestad: None. Funding National Institutes of Health (1K23DK106533)

Olive leaf extract supplementation improves the vascular and metabolic alterations associated with aging in Wistar rats

Olive leaves are rich in bioactive substances which exert anti-inflammatory, antioxidant, insulin-sensitizing and antihypertensive effects. The aim of this study was to analyze the possible beneficial effects of an olive leaf extract (OLE) rich in secoiridoids and phenolic compounds on the aging-induced metabolic and vascular alterations. Three experimental groups of rats were used: 3-month-old rats, 24-month-old rats and 24-month-old rats supplemented 21 days with OLE (100 mg/kg). Administration of OLE to aged rats decreased the weight of adrenal glands and prevented the aging-induced loss of body weight and muscle mass. In the serum, OLE reduced the circulating levels of LDL-cholesterol and IL-6 and increased the concentrations of leptin and adiponectin. In the liver OLE attenuated the decreased gene expression of SOD-1, GSR, GCK and GSK-3β and reduced the aging-induced overexpression of NOX-4, Alox-5, iNOS and TNF-α. In aorta segments, OLE prevented endothelial dysfunction and vascular insulin resistance and improved vasoconstriction in response to KCl and NA. Improvement in vascular function was associated with the attenuation of the alterations in the gene expression of COX-2, IL-6, GPx, NOX-1 and IL-10. In conclusion, OLE exerts anti-inflammatory and antioxidant effects in aged rats and attenuates the alterations in vascular function associated with aging.

Preliminary Evidence of Orthostatic Intolerance and Altered Cerebral Vascular Control Following Sport-Related Concussion.

Concussions have been shown to result in autonomic dysfunction and altered cerebral vascular function. We tested the hypothesis that concussed athletes (CA) would have altered cerebral vascular function during acute decreases and increases in blood pressure compared to healthy controls (HC). Ten CA (age: 20 ± 2 y, 7 females) and 10 HC (age: 21 ± 2 y, 6 females) completed 5 min of lower body negative pressure (LBNP; −40 mmHg) and 5 min of lower body positive pressure (LBPP; 20 mmHg). Protocols were randomized and separated by 10 min. Mean arterial pressure (MAP) and middle cerebral artery blood velocity (MCAv) were continuously recorded. Cerebral vascular resistance (CVR) was calculated as MAP/MCAv. Values are reported as change from baseline to the last minute achieved (LBNP) or 5 min (LBPP). There were no differences in baseline values between groups. During LBNP, there were no differences in the change for MAP (CA: −23 ± 18 vs. HC: −21 ± 17 cm/s; P = 0.80) or MCAv (CA: −13 ± 8 vs. HC: −18 ± 9 cm/s; P = 0.19). The change in CVR was different between groups (CA: −0.08 ± 0.26 vs. HC: 0.18 ± 0.24 mmHg/cm/s; P = 0.04). Total LBNP time was lower for CA (204 ± 92 s) vs. HC (297 ± 64 s; P = 0.04). During LBPP, the change in MAP was not different between groups (CA: 13 ± 6 vs. HC: 10 ± 7 mmHg; P = 0.32). The change in MCAv (CA: 7 ± 6 vs. HC: −4 ± 13 cm/s; P = 0.04) and CVR (CA: −0.06 ± 0.27 vs. HC: 0.38 ± 0.41 mmHg/cm/s; P = 0.03) were different between groups. CA exhibited impaired tolerance to LBNP and had a different cerebral vascular response to LBPP compared to HC.

Blunted hyperemic response to mental stress in young, non-Hispanic black men is not impacted by acute dietary nitrate supplementation.

Non-Hispanic black individuals suffer from an elevated prevalence of hypertension and cardiovascular disease (CVD) relative to other populations. This elevated disease risk is, in large part, related to impaired vascular function, secondary to reduced nitric oxide (NO) bioavailability. Emerging evidence suggests that dietary nitrate supplementation improves several cardiovascular parameters, including vascular function, in part by increased NO bioavailability. However, whether these findings extend to a population of black individuals is unknown. This study tested the hypothesis that forearm blood flow responses in young, non-Hispanic, black (BL) men during a mental stress challenge would be blunted relative to young, non-Hispanic, white (WH) men. We further hypothesized that acute dietary nitrate supplementation would improve this response in BL men. This study comprised two parts (phase 1 and phase 2). Phase 1 investigated the difference in blood flow responses between young, BL, and WH men. In contrast, phase 2 investigated the effect of acute nitrate supplementation on the responses in a subset of the BL men from phase 1. Eleven (nine for phase 2) BL and eight WH men (23 ± 3 vs. 24 ± 4 yr, respectively) participated in this double-blind, placebo-controlled, randomized, crossover study. During each visit, hemodynamic responses during 3 min of mental stress were assessed in the brachial artery using duplex Doppler ultrasound. Phase 1 was completed in one visit, whereas phase 2 was completed over two visits separated by ∼1 wk. During phase 2, data were collected before and 2-h postconsumption of a beverage either high in nitrate content or nitrate depleted. In phase 1, peak forearm blood flow (FBF; P < 0.001), total FBF (P < 0.01), and forearm vascular conductance (FVC; P < 0.001) were blunted in the BL. During phase 2, prebeverage responses were similar to phase 1 and were unaffected following beverage consumption (P > 0.05 vs. prebeverage for all variables). These data indicate that young, BL men have blunted microvascular vasodilatory responses to acute mental stress, which may not be altered following acute nitrate supplementation.NEW & NOTEWORTHY This study tested the hypothesis that non-Hispanic black (BL) men have a blunted forearm hyperemic response to mental stress, which would be augmented following acute nitrate supplementation. The increase in forearm blood flow during mental stress was attenuated in BL men and was not impacted by nitrate supplementation. This supports findings of altered vascular function in this population. This is especially important as BL experience a higher prevalence of stress, which contributes to CVD risk.

Cinnamaldehyde mitigates placental vascular dysfunction of gestational diabetes and protects from the associated fetal hypoxia by modulating placental angiogenesis, metabolic activity and oxidative stress

Gestational diabetes mellitus (GDM) is a major pregnancy-related disorder with an increasing prevalence worldwide. GDM is associated with altered placental vascular functions and has severe consequences for fetal growth. There is no commonly accepted medication for GDM due to safety considerations. Actions of the currently limited therapeutic options focus exclusively on lowering the blood glucose level without paying attention to the altered placental vascular reactivity and remodelling. We used the fat-sucrose diet/streptozotocin (FSD/STZ) rat model of GDM to explore the efficacy of cinnamaldehyde (Ci; 20 mg/kg/day), a promising antidiabetic agent for GDM, and glyburide/metformin-HCl (Gly/Met; 0.6 + 100 mg/kg/day), as a reference drug for treatment of GDM, on the placenta structure and function at term pregnancy after their oral intake one week before mating onward. Through genome-wide transcriptome, biochemical, metabolome, metal analysis and histopathology we obtained an integrated understanding of their effects. GDM resulted in maternal and fetal hyperglycemia, fetal hyperinsulinemia and placental dysfunction with subsequent fetal anemia, hepatic iron deficiency and high serum erythropoietin level, reflecting fetal hypoxia. Differentially-regulated genes were overrepresented for pathways of angiogenesis, metabolic transporters and oxidative stress. Despite Ci and Gly/Met effectively alleviated the maternal and fetal glycemia, only Ci offered substantial protection from GDM-associated placental vasculopathy and prevented the fetal hypoxia. This was explained by Ci’s impact on the molecular regulation of placental angiogenesis, metabolic activity and redox signaling. In conclusion, Ci provides a dual impact for the treatment of GDM at both maternal and fetal levels through its antidiabetic effect and the direct placental vasoprotective action. Lack of Gly/Met effectiveness to restore it’s impaired functionality demonstrates the vital role of the placenta in developing efficient medications for GDM.