scholarly journals ADMA: A Key Player in the Relationship between Vascular Dysfunction and Inflammation in Atherosclerosis

2020 ◽  
Vol 9 (9) ◽  
pp. 3026
Author(s):  
Laura Dowsett ◽  
Erin Higgins ◽  
Sarah Alanazi ◽  
Noha A. Alshuwayer ◽  
Fiona C. Leiper ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Vessel Wall ◽  
Vascular Dysfunction ◽  
Plasma Concentrations ◽  
Inflammatory Cells ◽  
Endothelial Activation ◽  
Major Cardiovascular Events ◽  
Clinical Literature ◽  
Increased Risk ◽  
Inflammatory Processes

Atherosclerosis is a chronic cardiovascular disease which increases risk of major cardiovascular events including myocardial infarction and stroke. Elevated plasma concentrations of asymmetric dimethylarginine (ADMA) have long been recognised as a hallmark of cardiovascular disease and are associated with cardiovascular risk factors including hypertension, obesity and hypertriglyceridemia. In this review, we discuss the clinical literature that link ADMA concentrations to increased risk of the development of atherosclerosis. The formation of atherosclerotic lesions relies on the interplay between vascular dysfunction, leading to endothelial activation and the accumulation of inflammatory cells, particularly macrophages, within the vessel wall. Here, we review the mechanisms through which elevated ADMA contributes to endothelial dysfunction, activation and reactive oxygen species (ROS) production; how ADMA may affect vascular smooth muscle phenotype; and finally whether ADMA plays a regulatory role in the inflammatory processes occurring within the vessel wall.

scholarly journals Incremental changes in QRS duration as predictor for cardiovascular disease: a 21-year follow-up of a randomly selected general population

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaojing Chen ◽  
Per-Olof Hansson ◽  
Erik Thunström ◽  
Zacharias Mandalenakis ◽  
Kenneth Caidahl ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
General Population ◽  
Cardiovascular Events ◽  
Population Sample ◽  
Cox Regression Analysis ◽  
Major Cardiovascular Events ◽  
Increased Risk ◽  
Qrs Duration ◽  
Group 1

AbstractThe QRS complex has been shown to be a prognostic marker in coronary artery disease. However, the changes in QRS duration over time, and its predictive value for cardiovascular disease in the general population is poorly studied. So we aimed to explore if increased QRS duration from the age of 50–60 is associated with increased risk of major cardiovascular events during a further follow-up to age 71. A random population sample of 798 men born in 1943 were examined in 1993 at 50 years of age, and re-examined in 2003 at age 60 and 2014 at age 71. Participants who developed cardiovascular disease before the re-examination in 2003 (n = 86) or missing value of QRS duration in 2003 (n = 127) were excluded. ΔQRS was defined as increase in QRS duration from age 50 to 60. Participants were divided into three groups: group 1: ΔQRS < 4 ms, group 2: 4 ms ≤ ΔQRS < 8 ms, group 3: ΔQRS ≥ 8 ms. Endpoints were major cardiovascular events. And we found compared with men in group 1 (ΔQRS < 4 ms), men with ΔQRS ≥ 8 ms had a 56% increased risk of MACE during follow-up to 71 years of age after adjusted for BMI, systolic blood pressure, smoking, hyperlipidemia, diabetes and heart rate in a multivariable Cox regression analysis (HR 1.56, 95% CI:1.07–2.27, P = 0.022). In conclusion, in this longitudinal follow-up over a decade QRS duration increased in almost two out of three men between age 50 and 60 and the increased QRS duration in middle age is an independent predictor of major cardiovascular events.

scholarly journals Plasma S1P links to hypertension and biomarkers of inflammation, metabolism and cardiovascular disease – findings from a translational investigation

2020 ◽  
Author(s):  
Amra Jujic ◽  
Frank Matthes ◽  
Lotte Vanherle ◽  
Henning Petzka ◽  
Marju Orho-Melander ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Systolic Blood Pressure ◽  
Immune Cell ◽  
Vascular Dysfunction ◽  
Plasma Concentrations ◽  
Human Study ◽  
Experimental Hypertension ◽  
Study Cohort ◽  
Markers Of Inflammation

Recent studies identified sphingosine-1-phosphate (S1P) as an important player in immune cell trafficking and vascular dysfunction contributing to the development and progression of overt hypertension. Although targeting S1P signaling revealed therapeutic potential in different experimental hypertension studies, validations of S1P-blood pressure associations in humans are lacking. In a translational approach, we explored the associations between plasma S1P, quantified using LC-MS, and blood pressure in a family-based study cohort (MOS) study, and in a longitudinally conducted murine hypertension cohort. In MOS, linear multivariate regression analyses showed that plasma S1P associates with increased systolic blood pressure. Study subjects with systolic blood pressure ≥ 140 mmHg presented with significantly higher S1P plasma concentrations compared to subjects with blood pressure ≤ 120 mmHg independent of age and sex. The S1P-blood pressure association was validated in a murine model where plasma S1P increased with systolic blood pressure. In a sub-sample of the human study population, proteomic profiling for markers of inflammation, metabolism and cardiovascular disease was carried out using proximity Extension Assays. Testing S1P associations revealed multiple significant interactions, some of them with marked sex-specificity. Amongst them, interleukin 18, which exerts apparent vascular and immune responses during hypertension and associates to adverse cardiovascular events, strongly correlates with plasma S1P concentrations in females but not males in both humans and mice. In vitro and ex vivo validation of S1P effects on endothelial and monocytic cells of murine or human origin and resistance arteries isolated from mice disclosed augmented expression of different vascular dysfunction and inflammation markers in response to exogenously added S1P. Taken together, our translational findings strongly suggest a link between plasma S1P and systolic blood pressure as well as several inflammation and cardiovascular disease biomarkers in humans, encouraging further studies to investigate S1Ps potential as a therapeutic target in hypertensive disease.

The Yin and Yang of High-density Lipoprotein and Atherosclerotic Cardiovascular Disease: Focusing on Functionality and Cholesterol Efflux to Reframe the HDL Hypothesis

2021 ◽  
Vol 28 ◽  
Author(s):  
Shiva Ganjali ◽  
Gerald F. Watts ◽  
Maciej Banach ◽  
Željko Reiner ◽  
Petr Nachtigal ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
Cholesterol Efflux ◽  
Association Studies ◽  
Plasma Concentrations ◽  
Density Lipoprotein ◽  
High Density ◽  
Atherosclerotic Cardiovascular Disease ◽  
Genome Wide Association Studies ◽  
Increased Risk

Abstract: The inverse relationship between low plasma high-density lipoprotein cholesterol (HDL-C) concentrations and increased risk of Atherosclerotic Cardiovascular Disease (ASCVD) is well-known. However, plasma HDL-C concentrations are highly variable in subjects with ASCVD. In clinical outcome trials, pharmacotherapies that increase HDL-C concentrations are not associated with a reduction in ASCVD events. A causal relationship between HDL-C and ASCVD has also been questioned by Mendelian randomization studies and genome-wide association studies of genetic variants associated with plasma HDL-C concentrations. The U-shaped association between plasma HDL-C concentrations and mortality observed in several epidemiological studies implicates both low and very high plasma HDL-C concentrations in the etiology of ASCVD and non-ASCVD mortality. These data do not collectively support a causal association between HDL-C and ASCVD risk. Therefore, the hypothesis concerning the association between HDL and ASCVD has shifted from focus on plasma concentrations to the concept of functionality, in particular cellular cholesterol efflux and HDL holoparticle transport. In this review, we focus on these new concepts and provide a new framework for understanding and testing the role of HDL in ASCVD.

scholarly journals FKBPL is associated with metabolic parameters and is a novel determinant of cardiovascular disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Andrzej S. Januszewski ◽  
Chris J. Watson ◽  
Vikki O’Neill ◽  
Kenneth McDonald ◽  
Mark Ledwidge ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Fasting Blood Glucose ◽  
Plasma Concentrations ◽  
Diabetic Group ◽  
Fk506 Binding Protein ◽  
Increased Risk ◽  
Echocardiographic Parameters ◽  
And Gender

AbstractType 2 diabetes (T2D) is associated with increased risk of cardiovascular disease (CVD). As disturbed angiogenesis and endothelial dysfunction are strongly implicated in T2D and CVD, we aimed to investigate the association between a novel anti-angiogenic protein, FK506-binding protein like (FKBPL), and these diseases. Plasma FKBPL was quantified by ELISA cross-sectionally in 353 adults, consisting of 234 T2D and 119 non–diabetic subjects with/without CVD, matched for age, BMI and gender. FKBPL levels were higher in T2D (adjusted mean: 2.03 ng/ml ± 0.90 SD) vs. non-diabetic subjects (adjusted mean: 1.79 ng/ml ± 0.89 SD, p = 0.02), but only after adjustment for CVD status. In T2D, FKBPL was negatively correlated with fasting blood glucose, HbA1c and diastolic blood pressure (DBP), and positively correlated with age, known diabetes duration, waist/hip ratio, urinary albumin/creatinine ratio (ACR) and fasting C-peptide. FKBPL plasma concentrations were increased in the presence of CVD, but only in the non-diabetic group (CVD: 2.02 ng/ml ± 0.75 SD vs. no CVD: 1.68 ng/ml ± 0.79 SD, p = 0.02). In non-diabetic subjects, FKBPL was positively correlated with an established biomarker for CVD, B-type Natriuretic Peptide (BNP), and echocardiographic parameters of diastolic dysfunction. FKBPL was a determinant of CVD in the non-diabetic group in addition to age, gender, total-cholesterol and systolic blood pressure (SBP). FKBPL may be a useful anti-angiogenic biomarker in CVD in the absence of diabetes and could represent a novel CVD mechanism.

scholarly journals ON THE VERSATILITY OF VON WILLEBRAND FACTOR

2013 ◽  
Vol 5 (1) ◽  
pp. e2013046 ◽  
Author(s):  
Antoine Rauch ◽  
Peter Lenting
Keyword(s):  
Structure Function ◽  
Von Willebrand Factor ◽  
Plasma Concentrations ◽  
Von Willebrand Disease ◽  
Physiological Relevance ◽  
Increased Risk ◽  
Inflammatory Processes ◽  
Thrombotic Complications ◽  
Von Willebrand ◽  
Willebrand Factor

Von Willebrand factor (VWF) is a large multimeric protein, the function of which has been demonstrated to be pivotal to the haemostatic system. Indeed, quantitative and/or qualitative abnormalities of VWF are associated with the bleeding disorder Von Willebrand disease (VWD). Moreover, increased plasma concentrations of VWF have been linked to an increased risk for thrombotic complications. In the previous decades, many studies have contributed to our understanding of how VWF is connected to the haemostatic system, particularly with regard to structure-function relationships. Interactive sites for important ligands of VWF (such as factor VIII, collagen, glycoprotein Iba, integrin aIIbb3 and protease ADAMTS13) have been identified, and mutagenesis studies have confirmed the physiological relevance of the interactions between VWF and these ligands.  However, we have also become aware that VWF has a more versatile character than previously thought, given its potential role in various non-hemostatic processes, like intimal thickening, tumor cell apoptosis and inflammatory processes. In the presence review, a summary of our knowledge on VWF structure-function relationships is provided in the context of the "classical" haemostatic task of VWF and in perspective of pathological processes beyond haemostasis.

scholarly journals Programming of Vascular Dysfunction in the Intrauterine Milieu of Diabetic Pregnancies

2018 ◽  
Vol 19 (11) ◽  
pp. 3665 ◽  
Author(s):  
Nada Sallam ◽  
Victoria Palmgren ◽  
Radha Singh ◽  
Cini John ◽  
Jennifer Thompson
Keyword(s):  
Nitric Oxide ◽  
Diabetes Mellitus ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Gestational Diabetes ◽  
Vascular Dysfunction ◽  
Endothelial Activation ◽  
Intrauterine Environment ◽  
Cox 2 ◽  
Diabetic Mothers

With the rising global tide of obesity, gestational diabetes mellitus (GDM) burgeoned into one of the most common antenatal disorders worldwide. Macrosomic babies born to diabetic mothers are more likely to develop risk factors for cardiovascular disease (CVD) before they reach adulthood. Rodent studies in offspring born to hyperglycemic pregnancies show vascular dysfunction characterized by impaired nitric oxide (NO)-mediated vasodilation and increased production of contractile prostanoids by cyclooxygenase 2 (COX-2). Vascular dysfunction is a key pathogenic event in the progression of diabetes-related vascular disease, primarily attributable to glucotoxicity. Therefore, glucose-induced vascular injury may stem directly from the hyperglycemic intrauterine environment of GDM pregnancy, as evinced by studies showing endothelial activation and inflammation at birth or in childhood in offspring born to GDM mothers. This review discusses potential mechanisms by which intrauterine hyperglycemia programs dysfunction in the developing vasculature.

scholarly journals Prevalence of metabolic syndrome within hypertensive population and the risk of developing atherosclerotic cardiovascular diseases

2015 ◽  
Vol 10 (2) ◽  
pp. 187-194
Author(s):  
Gabriel Cristian BEJAN ◽  
◽  
Dumitru MATEI ◽  
Adela IANCU ◽  
◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Cardiovascular Diseases ◽  
Urban Areas ◽  
Cardiovascular Events ◽  
Insulin Resistance Syndrome ◽  
Major Cardiovascular Events ◽  
Hypertensive Population ◽  
Increased Risk ◽  
Atherosclerotic Cardiovascular Diseases

Metabolic syndrome, also called insulin resistance syndrome or excess of catecholamines, is represented by several cardiometabolic factors that result in increased incidence of cardiovascular disease and type 2 diabetes. Due to sedentary lifestyle and hypercaloric food, with a high percent of saturated fats and carbohydrates, that characterize modern lifestyle of the population, especially in urban areas, the prevalence of metabolic syndrome recorded an ascending slope that makes it a very topical issue for the medical world. During the years 2013-2014 we conducted an observational study on a sample of 111 hypertensive patients without major cardiovascular events such as myocardial infarction or stroke, with age between 48 and 83 years, in whom we determined the prevalence of metabolic syndrome and cardiovascular disease. The survey results showed an increased prevalence of metabolic syndrome, considering that we related to a hypertensive population, and an increased risk of non-fatal atherosclerotic cardiovascular diseases in men and fatal cardiovascular events in next 10 years especially for women.

scholarly journals Lipoprotein(a)

2021 ◽  
Author(s):  
Florian Kronenberg
Keyword(s):  
Cardiovascular Disease ◽  
Genetic Variants ◽  
Cardiovascular Events ◽  
Ldl Cholesterol ◽  
Single Gene ◽  
Genetic Regulation ◽  
Plasma Concentrations ◽  
Lipoprotein A ◽  
Increased Risk ◽  
Peripheral Arterial

AbstractLipoprotein(a) [Lp(a)] is an atherogenic lipoprotein with a strong genetic regulation. Up to 90% of the concentrations are explained by a single gene, the LPA gene. The concentrations show a several-hundred-fold interindividual variability ranging from less than 0.1 mg/dL to more than 300 mg/dL. Lp(a) plasma concentrations above 30 mg/dL and even more above 50 mg/dL are associated with an increased risk for cardiovascular disease including myocardial infarction, stroke, aortic valve stenosis, heart failure, peripheral arterial disease, and all-cause mortality. Since concentrations above 50 mg/dL are observed in roughly 20% of the Caucasian population and in an even higher frequency in African-American and Asian-Indian ethnicities, it can be assumed that Lp(a) is one of the most important genetically determined risk factors for cardiovascular disease.Carriers of genetic variants that are associated with high Lp(a) concentrations have a markedly increased risk for cardiovascular events. Studies that used these genetic variants as a genetic instrument to support a causal role for Lp(a) as a cardiovascular risk factor are called Mendelian randomization studies. The principle of this type of studies has been introduced and tested for the first time ever with Lp(a) and its genetic determinants.There are currently no approved pharmacologic therapies that specifically target Lp(a) concentrations. However, some therapies that target primarily LDL cholesterol have also an influence on Lp(a) concentrations. These are mainly PCSK9 inhibitors that lower LDL cholesterol by 60% and Lp(a) by 25–30%. Furthermore, lipoprotein apheresis lowers both, Lp(a) and LDL cholesterol, by about 60–70%. Some sophisticated study designs and statistical analyses provided support that lowering Lp(a) by these therapies also lowers cardiovascular events on top of the effect caused by lowering LDL cholesterol, although this was not the main target of the therapy. Currently, new therapies targeting RNA such as antisense oligonucleotides (ASO) or small interfering RNA (siRNA) against apolipoprotein(a), the main protein of the Lp(a) particle, are under examination and lower Lp(a) concentrations up to 90%. Since these therapies specifically lower Lp(a) concentrations without influencing other lipoproteins, they will serve the last piece of the puzzle whether a decrease of Lp(a) results also in a decrease of cardiovascular events.

Sign in / Sign up

Export Citation Format

Share Document