Introduction to the Biochemical Society Focused Meeting on Diet and Cardiovascular Health: Chylomicron Remnants and Their Emerging Roles in Vascular Dysfunction in Atherosclerosis

2007 ◽  
Vol 35 (3) ◽  
pp. 437-439 ◽  
Author(s):  
K.M. Botham ◽  
C.P.D. Wheeler-Jones
Keyword(s):  
Vascular Function ◽  
Cardiovascular Health ◽  
Vascular Dysfunction ◽  
Developed Countries ◽  
Dietary Lipids ◽  
Blood Cholesterol ◽  
Direct Role ◽  
Cholesterol Levels ◽  
The Metabolic Syndrome ◽  
Chylomicron Remnants

Although it has been known for many years that dietary lipids influence the development of atherosclerosis, in the past this has been attributed to their effects on blood cholesterol levels. Recent work, however, has shown that CMRs (chylomicron remnants), the lipoproteins which carry dietary lipids in the blood, potentially have a direct role in initiating atherogenesis by influencing vascular function. The Diet and Cardiovascular Health: Chylomicron Remnants and Their Emerging Roles in Vascular Dysfunction in Atherosclerosis Meeting focused attention on studies which have shown that CMRs influence vascular function via interactions with cells of the artery wall, including endothelial cells and macrophages, and also highlighted the part played by CMRs in the development of premature atherosclerosis in conditions such as the metabolic syndrome, which are an increasing cause of heart disease in developed countries.

scholarly journals ET-1 as a Sex-Specific Mechanism Impacting Age-Related Changes in Vascular Function

2021 ◽  
Vol 2 ◽  
Author(s):  
Andrew V. Kuczmarski ◽  
Laura M. Welti ◽  
Kerrie L. Moreau ◽  
Megan M. Wenner
Keyword(s):  
Sex Differences ◽  
Vascular Function ◽  
Cardiovascular Health ◽  
Vascular Dysfunction ◽  
Developed Countries ◽  
Therapeutic Interventions ◽  
Vascular Aging ◽  
Cvd Risk ◽  
Men And Women ◽  
Age Related

Aging is a primary risk factor for cardiovascular disease (CVD), which is the leading cause of death in developed countries. Globally, the population of adults over the age of 60 is expected to double by the year 2050. CVD prevalence and mortality rates differ between men and women as they age in part due to sex-specific mechanisms impacting the biological processes of aging. Measures of vascular function offer key insights into cardiovascular health. Changes in vascular function precede changes in CVD prevalence rates in men and women and with aging. A key mechanism underlying these changes in vascular function is the endothelin (ET) system. Studies have demonstrated sex and sex hormone effects on endothelin-1 (ET-1), and its receptors ETA and ETB. However, with aging there is a dysregulation of this system resulting in an imbalance between vasodilation and vasoconstriction. Thus, ET-1 may play a role in the sex differences observed with vascular aging. While most research has been conducted in pre-clinical animal models, we describe more recent translational data in humans showing that the ET system is an important regulator of vascular dysfunction with aging and acts through sex-specific ET receptor mechanisms. In this review, we present translational evidence (cell, tissue, animal, and human) that the ET system is a key mechanism regulating sex-specific changes in vascular function with aging, along with therapeutic interventions to reduce ET-mediated vascular dysfunction associated with aging. More knowledge on the factors responsible for the sex differences with vascular aging allow for optimized therapeutic strategies to attenuate CVD risk in the expanding aging population.

scholarly journals Role of the CYP4A/20-HETE pathway in vascular dysfunction of the Dahl salt-sensitive rat

2013 ◽  
Vol 124 (12) ◽  
pp. 695-700 ◽  
Author(s):  
Kathleen M. Lukaszewicz ◽  
Julian H. Lombard
Keyword(s):  
Animal Model ◽  
Vascular Function ◽  
Genetic Model ◽  
Vascular Dysfunction ◽  
Human Subjects ◽  
Brown Norway ◽  
Direct Role ◽  
Norway Rat ◽  
Cytochrome P450 4A

20-HETE (20-hydroxyeicosatetraenoic acid), a vasoconstrictor metabolite of arachidonic acid formed through the action of CYP4A (cytochrome P450-4A) in vascular smooth muscle cells, has been implicated in the development of hypertension and vascular dysfunction. There have been a number of reports in human subjects demonstrating an association between elevated urinary excretion of 20-HETE and hypertension, as well as increased 20-HETE production and vascular dysfunction. The Dahl SS (salt-sensitive) rat is a genetic model of salt-sensitive hypertension that exhibits vascular dysfunction, even when maintained on a normal-salt diet and before the development of hypertension. This mini-review highlights our current research on the role of CYP4A and 20-HETE in the vascular dysfunction of the Dahl SS rat. In our studies, the SS rat is compared with the consomic SS-5BN rat, having chromosome 5 from the salt-resistant Brown Norway rat (carrying all CYP4A genes) introgressed on to the SS genetic background. Our laboratory has demonstrated restoration of normal vascular function in the SS rat with inhibition of the CYP4A/20-HETE pathway, suggesting a direct role for this pathway in the vascular dysfunction in this animal model. Our studies have also shown that the SS rat has an up-regulated CYP4A/20-HETE pathway within their cerebral vasculature compared with the SS-5BN consomic rat, which causes endothelial dysfunction through the production of ROS (reactive oxygen species). Our data shows that ROS influences the expression of the CYP4A/20-HETE pathway in the SS rat in a feed-forward mechanism whereby elevated ROS stimulates production of 20-HETE. The presence of this vicious cycle offers a possible explanation for the spiralling effects of elevated 20-HETE on the development of vascular dysfunction in this animal model.

scholarly journals New Technologies With Increased Precision Improve Understanding of Endothelial Cell Heterogeneity in Cardiovascular Health and Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Ashley Dawson ◽  
Yidan Wang ◽  
Yanming Li ◽  
Scott A. LeMaire ◽  
Ying H. Shen
Keyword(s):  
Vascular Function ◽  
Cardiovascular Health ◽  
New Technologies ◽  
Vascular Dysfunction ◽  
Vascular Wall ◽  
Vascular Health ◽  
Different Types ◽  
Endothelial Cell Heterogeneity ◽  
Health And Disease ◽  
Vessel Integrity

Endothelial cells (ECs) are vital for blood vessel integrity and have roles in maintaining normal vascular function, healing after injury, and vascular dysfunction. Extensive phenotypic heterogeneity has been observed among ECs of different types of blood vessels in the normal and diseased vascular wall. Although ECs with different phenotypes can share common functions, each has unique features that may dictate a fine-tuned role in vascular health and disease. Recent studies performed with single-cell technology have generated powerful information that has significantly improved our understanding of EC biology. Here, we summarize a variety of EC types, states, and phenotypes recently identified by using new, increasingly precise techniques in transcriptome analysis.

Obesity, Adipose Tissue and Vascular Dysfunction

2021 ◽  
Vol 128 (7) ◽  
pp. 951-968 ◽  
Author(s):  
Mascha Koenen ◽  
Michael A. Hill ◽  
Paul Cohen ◽  
James R. Sowers
Keyword(s):  
Adipose Tissue ◽  
Cardiovascular Diseases ◽  
Vascular Function ◽  
Cardiovascular Health ◽  
Immune Cell ◽  
Vascular Dysfunction ◽  
The United States ◽  
Overweight And Obesity ◽  
Perivascular Adipose Tissue ◽  
Adipose Tissue Depots

Cardiovascular diseases are the leading cause of death worldwide. Overweight and obesity are strongly associated with comorbidities such as hypertension and insulin resistance, which collectively contribute to the development of cardiovascular diseases and resultant morbidity and mortality. Forty-two percent of adults in the United States are obese, and a total of 1.9 billion adults worldwide are overweight or obese. These alarming numbers, which continue to climb, represent a major health and economic burden. Adipose tissue is a highly dynamic organ that can be classified based on the cellular composition of different depots and their distinct anatomical localization. Massive expansion and remodeling of adipose tissue during obesity differentially affects specific adipose tissue depots and significantly contributes to vascular dysfunction and cardiovascular diseases. Visceral adipose tissue accumulation results in increased immune cell infiltration and secretion of vasoconstrictor mediators, whereas expansion of subcutaneous adipose tissue is less harmful. Therefore, fat distribution more than overall body weight is a key determinant of the risk for cardiovascular diseases. Thermogenic brown and beige adipose tissue, in contrast to white adipose tissue, is associated with beneficial effects on the vasculature. The relationship between the type of adipose tissue and its influence on vascular function becomes particularly evident in the context of the heterogenous phenotype of perivascular adipose tissue that is strongly location dependent. In this review, we address the abnormal remodeling of specific adipose tissue depots during obesity and how this critically contributes to the development of hypertension, endothelial dysfunction, and vascular stiffness. We also discuss the local and systemic roles of adipose tissue derived secreted factors and increased systemic inflammation during obesity and highlight their detrimental impact on cardiovascular health.

Targeting the Cholesterol Paradigm in the Risk Reduction for Atherosclerotic Cardiovascular Disease: Does the Mechanism of Action of Pharmacotherapy Matter for Clinical Outcomes?

2021 ◽  
pp. 107424842110236
Author(s):  
Ruihai Zhou ◽  
George A. Stouffer ◽  
Sidney C. Smith
Keyword(s):  
Cardiovascular Disease ◽  
Clinical Outcomes ◽  
Mechanism Of Action ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Blood Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitors ◽  
Cholesterol Lowering ◽  
Cholesterol Levels

Hypercholesterolemia is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD). Low-density lipoprotein cholesterol (LDL-C) has been labeled as “bad” cholesterol and high-density lipoprotein cholesterol (HDL-C) as “good” cholesterol. The prevailing hypothesis is that lowering blood cholesterol levels, especially LDL-C, reduces vascular deposition and retention of cholesterol or apolipoprotein B (apoB)-containing lipoproteins which are atherogenic. We review herein the clinical trial data on different pharmacological approaches to lowering blood cholesterol and propose that the mechanism of action of cholesterol lowering, as well as the amplitude of cholesterol reduction, are critically important in leading to improved clinical outcomes in ASCVD. The effects of bile acid sequestrants, fibrates, niacin, cholesteryl ester transfer protein (CETP) inhibitors, apolipoprotein A-I and HDL mimetics, apoB regulators, acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitors, cholesterol absorption inhibitors, statins, and proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors, among other strategies are reviewed. Clinical evidence supports that different classes of cholesterol lowering or lipoprotein regulating approaches yielded variable effects on ASCVD outcomes, especially in cardiovascular and all-cause mortality. Statins are the most widely used cholesterol lowering agents and have the best proven cardiovascular event and survival benefits. Manipulating cholesterol levels by specific targeting of apoproteins or lipoproteins has not yielded clinical benefit. Understanding why lowering LDL-C by different approaches varies in clinical outcomes of ASCVD, especially in survival benefit, may shed further light on our evolving understanding of how cholesterol and its carrier lipoproteins are involved in ASCVD and aid in developing effective pharmacological strategies to improve the clinical outcomes of ASCVD.

scholarly journals Association between the Mediterranean lifestyle, metabolic syndrome and mortality: a whole-country cohort in Spain

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Mercedes Sotos-Prieto ◽  
Rosario Ortolá ◽  
Miguel Ruiz-Canela ◽  
Esther Garcia-Esquinas ◽  
David Martínez-Gómez ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Cardiovascular Mortality ◽  
Cardiovascular Health ◽  
Total Mortality ◽  
Hdl Cholesterol ◽  
Cardiometabolic Health ◽  
The Metabolic Syndrome ◽  
Mediterranean Countries ◽  
Low Hdl ◽  
The Mediterranean

Abstract Background Evidence is limited about the joint health effects of the Mediterranean lifestyle on cardiometabolic health and mortality. The aim of this study was to evaluate the association of the Mediterranean lifestyle with the frequency of the metabolic syndrome (MS) and the risk of all-cause and cardiovascular mortality in Spain. Methods Data were taken from ENRICA study, a prospective cohort of 11,090 individuals aged 18+ years, representative of the population of Spain, who were free of cardiovascular disease (CVD) and diabetes at 2008–2010 and were followed-up to 2017. The Mediterranean lifestyle was assessed at baseline with the 27-item MEDLIFE index (with higher score representing better adherence). Results Compared to participants in the lowest quartile of MEDLIFE, those in the highest quartile had a multivariable-adjusted odds ratio 0.73 (95% confidence interval (CI) 0.5, 0.93) for MS, 0.63. (0.51, 0.80) for abdominal obesity, and 0.76 (0.63, 0.90) for low HDL-cholesterol. Similarly, a higher MELDIFE score was associated with lower HOMA-IR and highly-sensitivity C-reactive protein (P-trend < 0.001). During a mean follow-up of 8.7 years, 330 total deaths (74 CVD deaths) were ascertained. When comparing those in highest vs. lowest quartile of MEDLIFE, the multivariable-adjusted hazard ratio (95% CI) was 0.58 (0.37, 0.90) for total mortality and 0.33 (0.11, 1.02) for cardiovascular mortality. Conclusions The Mediterranean lifestyle was associated with lower frequency of MS and reduced all-cause mortality in Spain. Future studies should determine if this also applies to other Mediterranean countries, and also improve cardiovascular health outside the Mediterranean basin.

scholarly journals Gestational Diabetes Mellitus Treatment Schemes Modify Maternal Plasma Cholesterol Levels Dependent to Women´s Weight: Possible Impact on Feto-Placental Vascular Function

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 506 ◽  
Author(s):  
Susana Contreras-Duarte ◽  
Lorena Carvajal ◽  
María Jesús Garchitorena ◽  
Mario Subiabre ◽  
Bárbara Fuenzalida ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Vascular Function ◽  
Plasma Cholesterol ◽  
Umbilical Vein ◽  
Maternal Plasma ◽  
Maternal Weight ◽  
Cholesterol Levels ◽  
The Impact

Gestational diabetes mellitus (GDM) associates with fetal endothelial dysfunction (ED), which occurs independently of adequate glycemic control. Scarce information exists about the impact of different GDM therapeutic schemes on maternal dyslipidemia and obesity and their contribution to the development of fetal-ED. The aim of this study was to evaluate the effect of GDM-treatments on lipid levels in nonobese (N) and obese (O) pregnant women and the effect of maternal cholesterol levels in GDM-associated ED in the umbilical vein (UV). O-GDM women treated with diet showed decreased total cholesterol (TC) and low-density lipoproteins (LDL) levels with respect to N-GDM ones. Moreover, O-GDM women treated with diet in addition to insulin showed higher TC and LDL levels than N-GDM women. The maximum relaxation to calcitonin gene-related peptide of the UV rings was lower in the N-GDM group compared to the N one, and increased maternal levels of TC were associated with even lower dilation in the N-GDM group. We conclude that GDM-treatments modulate the TC and LDL levels depending on maternal weight. Additionally, increased TC levels worsen the GDM-associated ED of UV rings. This study suggests that it could be relevant to consider a specific GDM-treatment according to weight in order to prevent fetal-ED, as well as to consider the possible effects of maternal lipids during pregnancy.

scholarly journals Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

2021 ◽  
Vol 22 (3) ◽  
pp. 1296
Author(s):  
Yue Ruan ◽  
Subao Jiang ◽  
Adrian Gericke
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Therapeutic Strategies ◽  
Vision Impairment ◽  
Age Related Macular Degeneration ◽  
Oxygen Species ◽  
Age Related

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.

scholarly journals Biomarker-estimated flavan-3-ol intake is associated with lower blood pressure in cross-sectional analysis in EPIC Norfolk

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Javier I. Ottaviani ◽  
Abigail Britten ◽  
Debora Lucarelli ◽  
Robert Luben ◽  
Angela A. Mulligan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Vascular Function ◽  
Cardiovascular Health ◽  
Vascular Diseases ◽  
Inverse Association ◽  
Cvd Risk ◽  
Lower Systolic Blood Pressure ◽  
Cross Sectional ◽  
Salt Reduction

Abstract Flavan-3-ols are a group of bioactive compounds that have been shown to improve vascular function in intervention studies. They are therefore of great interest for the development of dietary recommendation for the prevention of cardio-vascular diseases. However, there are currently no reliable data from observational studies, as the high variability in the flavan-3-ol content of food makes it difficult to estimate actual intake without nutritional biomarkers. In this study, we investigated cross-sectional associations between biomarker-estimated flavan-3-ol intake and blood pressure and other CVD risk markers, as well as longitudinal associations with CVD risk in 25,618 participants of the European Prospective Investigation into Cancer (EPIC) Norfolk cohort. High flavan-3-ol intake, achievable as part of an habitual diet, was associated with a significantly lower systolic blood pressure (− 1.9 (− 2.7; − 1.1) mmHg in men and − 2.5 (− 3.3; − 1.8) mmHg in women; lowest vs highest decile of biomarker), comparable to adherence to a Mediterranean Diet or moderate salt reduction. Subgroup analyses showed that hypertensive participants had stronger inverse association between flavan-3-ol biomarker and systolic blood pressure when compared to normotensive participants. Flavanol intake could therefore have a role in the maintenance of cardiovascular health on a population scale.

Dietary lipids and gene expression

2004 ◽  
Vol 32 (6) ◽  
pp. 999-1002 ◽  
Author(s):  
H.M. Roche
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Transcription Factors ◽  
Fatty Acid ◽  
Regulatory Element ◽  
Nuclear Factor Κb ◽  
Dietary Lipids ◽  
Dietary Fatty Acids ◽  
Dietary Fatty Acid ◽  
The Metabolic Syndrome

Nutrition is a key environmental factor that is particularly involved in the pathogenesis and progression of several polygenic, diet-related diseases. Nutrigenomics refers to the interaction between nutrition and the human genome. Dietary fatty acids interact with multiple nutrient-sensitive transcription factors. This explains the molecular basis of some of the health effects associated with altered dietary fatty acid composition. The metabolic syndrome is a very common condition, characterized by insulin resistance, abdominal obesity, dyslipidaemia and hypertension. It often precedes Type 2 diabetes mellitus, and is associated with a greater risk of cardiovascular disease. Several lines of evidence suggest that the interaction between nutrient-derived metabolic stressors and pro-inflammatory signals play an important role in the aetiology of insulin resistance and the development of the metabolic syndrome. This paper will address the interaction between several nutrient-sensitive transcription factors, including SREBP (sterol-regulatory-element-binding protein) and NFκB (nuclear factor κB), demonstrating how this interaction may be altered with dietary fatty acid interventions.

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