scholarly journals Environmental Contaminants Acting as Endocrine Disruptors Modulate Atherogenic Processes: New Risk Factors for Cardiovascular Diseases in Women?

2021 ◽  
Author(s):  
Silvia Migliaccio ◽  
Viviana M Bimonte ◽  
Zein Mersini Besharat ◽  
Claudia Sabato ◽  
Clara Crescioli ◽  
...  
Keyword(s):  
Endocrine Disruptors ◽  
Successful Aging ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Vascular Diseases ◽  
Unhealthy Lifestyle ◽  
Age Related ◽  
Increased Risk ◽  
Artery Disease ◽  
Cardio Vascular

The number of aged individuals is increasing worldwide, rendering essential the comprehension of pathophysiological mechanisms of age-related alterations, that could facilitate the development of interventions contributing to “successful aging” and improvement of quality of life. Cardio-vascular diseases (CVD) include pathologies affecting heart or blood vessels, such as hyperten-sion, peripheral artery disease and coronary heart disease. Indeed, age-associated modifications in body composition, hormonal, nutritional and metabolic factors, as well as a decline in physical activity are all involved in the increased risk of developing atherogenic alterations raising the risk of CVD development. Several factors have been claimed to play a role in the alterations observed in muscle and endothelial cells and leading to increased CVD, such as genetic pattern, smoking, unhealthy lifestyle. Moreover, a difference in the risk of these diseases in women and men has been reported. Interestingly, in the last decades attention has been focused on a potential role of several pollutants which disrupt human health by interfering with hormonal pathways, and more specifically in non-communicable diseases such as obesity, diabetes and CVD. This review will focus on the potential alteration induced by Endocrine Disruptors (Eds) in the attempt to characterize a potential role in the cellular and molecular mechanisms involved in the atheromatic process and CVD progression.

scholarly journals Environmental Contaminants Acting as Endocrine Disruptors Modulate Atherogenic Processes: New Risk Factors for Cardiovascular Diseases in Women?

Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 44
Author(s):  
Silvia Migliaccio ◽  
Viviana M. Bimonte ◽  
Zein Mersini Besharat ◽  
Claudia Sabato ◽  
Andrea Lenzi ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Endocrine Disruptors ◽  
Successful Aging ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Unhealthy Lifestyle ◽  
Age Related ◽  
Increased Risk ◽  
Artery Disease

The number of aged individuals is increasing worldwide, rendering essential the comprehension of pathophysiological mechanisms of age-related alterations, which could facilitate the development of interventions contributing to “successful aging” and improving quality of life. Cardiovascular diseases (CVD) include pathologies affecting the heart or blood vessels, such as hypertension, peripheral artery disease and coronary heart disease. Indeed, age-associated modifications in body composition, hormonal, nutritional and metabolic factors, as well as a decline in physical activity are all involved in the increased risk of developing atherogenic alterations that raise the risk of CVD development. Several factors have been reported to play a role in the alterations observed in muscle and endothelial cells and that lead to increased CVD, such as genetic pattern, smoking and unhealthy lifestyle. Moreover, a difference in the risk of these diseases in women and men has been reported. Interestingly, in the past decades attention has been focused on a potential role of several pollutants that disrupt human health by interfering with hormonal pathways, and more specifically in non-communicable diseases such as obesity, diabetes and CVD. This review will focus on the potential alteration induced by Endocrine Disruptors (Eds) in the attempt to characterize a potential role in the cellular and molecular mechanisms involved in the atheromatous degeneration process and CVD progression.

Inflammatory Molecular Mediators and Pathways Involved in Vascular Aging and Stroke: A Comprehensive Review

2021 ◽  
Vol 28 ◽  
Author(s):  
Amro M. Soliman ◽  
Srijit Das ◽  
Pasuk Mahakkanukrauh
Keyword(s):  
Drug Targets ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Vascular Diseases ◽  
Vascular Aging ◽  
Inflammatory Conditions ◽  
Age Related ◽  
Cardiovascular Pathologies ◽  
Potential Drug Targets

: There is an increase in the incidence of cardiovascular diseases with aging and it is one of the leading causes of death worldwide. The main cardiovascular pathologies include atherosclerosis, stroke, myocardial infarction, hypertension and stroke. Chronic inflammation is one of the significant contributors to the age-related vascular diseases. Therefore, it is important to understand the molecular mechanisms of the persistent inflammatory conditions occurring in the blood vessels as well as the signaling pathways involved. Herein, we performed an extant search of literature involving PubMed, ISI, WoS and Scopus databases for retrieving all relevant articles with the most recent findings illustrating the potential role of various inflammatory mediators along with their proposed activated pathways in the pathogenesis and progression of vascular aging. We also highlight the major pathways contributing to age-related vascular disorders. The outlined molecular mechanisms, pathways and mediators of vascular aging represent potential drug targets that can be utilized to inhibit and/or slow the pathogenesis and progression of vascular aging.

The Role of Vascular Aging in Atherosclerotic Plaque Development and Vulnerability

2019 ◽  
Vol 25 (29) ◽  
pp. 3098-3111 ◽  
Author(s):  
Luca Liberale ◽  
Giovanni G. Camici
Keyword(s):  
Atherosclerotic Plaque ◽  
Molecular Mechanisms ◽  
Driving Forces ◽  
Plaque Burden ◽  
Vascular Aging ◽  
Age Related ◽  
Plaque Development ◽  
Increased Risk ◽  
The Impact ◽  
Over Time

Background: The ongoing demographical shift is leading to an unprecedented aging of the population. As a consequence, the prevalence of age-related diseases, such as atherosclerosis and its thrombotic complications is set to increase in the near future. Endothelial dysfunction and vascular stiffening characterize arterial aging and set the stage for the development of cardiovascular diseases. Atherosclerotic plaques evolve over time, the extent to which these changes might affect their stability and predispose to sudden complications remains to be determined. Recent advances in imaging technology will allow for longitudinal prospective studies following the progression of plaque burden aimed at better characterizing changes over time associated with plaque stability or rupture. Oxidative stress and inflammation, firmly established driving forces of age-related CV dysfunction, also play an important role in atherosclerotic plaque destabilization and rupture. Several genes involved in lifespan determination are known regulator of redox cellular balance and pre-clinical evidence underlines their pathophysiological roles in age-related cardiovascular dysfunction and atherosclerosis. Objective: The aim of this narrative review is to examine the impact of aging on arterial function and atherosclerotic plaque development. Furthermore, we report how molecular mechanisms of vascular aging might regulate age-related plaque modifications and how this may help to identify novel therapeutic targets to attenuate the increased risk of CV disease in elderly people.

Homocysteine and thrombosis: from basic science to clinical evidence

2005 ◽  
Vol 94 (11) ◽  
pp. 907-915 ◽  
Author(s):  
Jan Brożek ◽  
Andrzej Szczeklik ◽  
Anetta Undas
Keyword(s):  
Molecular Mechanisms ◽  
Platelet Reactivity ◽  
Current Evidence ◽  
Factor V ◽  
Dna Hypomethylation ◽  
Homocysteine Concentration ◽  
Increased Risk ◽  
Venous Thromboembolic Events ◽  
Venous Thromboembolic ◽  
Artery Disease

SummaryHomocysteine is a sulfhydryl-containing amino acid formed during the metabolism of methionine. Rapidly accumulating evidence links elevated homocysteine levels to thrombosis via several mechanisms such as increased tissue factor expression, attenuated anticoagulant processes, enhanced platelet reactivity, increased thrombin generation, augmented factor V activity, impaired fibrinolytic potential, and vascular injury, including endothelial dysfunction. Molecular mechanisms underlying prothrombotic actions of homocysteine are incompletely understood and involve oxidative stress, DNA hypomethylation, and proinflammatory effects. Current evidence from retrospective and prospective studies supports the concept that higher total plasma homocysteine concentration is associated with increased risk of coronary artery disease, stroke, and venous thromboembolism. Hyperhomocysteinemia is currently considered a relatively weak prothrombotic factor. It is still unclear whether administration of vitamins, that reduce homocysteine levels acting as cofactors of the enzymes involved in the methionine metabolism, may decrease the risk of arterial and/or venous thromboembolic events. Ongoing clinical trials might help clarify this issue.

Abstract 491: Detection of Subclinical Coronary Artery Disease by Calcium Score in Patients With Atrial Fibrillation: Potential Clinical Implications

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Kongkiat Chaikriangkrai ◽  
Miguel Valderrabano ◽  
Sayf Khaleel Bala ◽  
Sama Alchalabi ◽  
Edward Graviss ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Vascular Diseases ◽  
Calcium Score ◽  
Clinical Implications ◽  
Therapeutic Implications ◽  
Increased Risk ◽  
Original Definition ◽  
Artery Disease

Background: Clinical implications of detecting subclinical coronary artery disease (CAD) in patients with atrial fibrillation (AF) are unclear. Methods: A total of 430 AF patients (age 63 ± 10 y, 65% male, 62% hypertensive, 16% diabetic, 42% dyslipidemic) without known CAD undergoing pre-procedural CT for catheter ablation were included. We evaluated the change in: 1) numbers of patients with CACS-diagnosed CAD who could potentially be on statin. 2) CHA2DS2-VASc score after incorporating CACS>100 (related to increased risk of stroke) into the original definition of vascular diseases who could potentially be on anticoagulants. Results: 1) Prevalence of subclinical CAD (CACS>0) was 74% (319/430) and 25% (106/430) had CACS>100. There were 62% (267/430) who were not on statin. Of these patients, 71% (190/267) had subclinical CAD while 21% (34/163) of statin users had CACS of 0. 2) The median original CHA2DS2-VASc score was 2. After incorporating CACS>100 into the original score, 24% (18/75) with the original score of 0 had the score changed to 1 (7/35 in persistent AF [PST-AF] and 11/40 in paroxysmal AF [PRX-AF]) (figure A) and 17% (22/131) with the original score of 1 had the score changed to ≥ 2 (10/83 in PST-AF and 12/48 in PRX-AF) (figure B). PRX-AF had more frequent increase in CHA2DS2-VASc score than PST-AF (p=0.035)(figure C). Conclusion: In AF patients without known history of CAD, detecting subclinical CAD by CACS potentially has important therapeutic implications for prevention forprogression of CAD and stroke.

scholarly journals p16INK4a deficiency promotes IL-4–induced polarization and inhibits proinflammatory signaling in macrophages

Blood ◽  
2011 ◽  
Vol 118 (9) ◽  
pp. 2556-2566 ◽  
Author(s):  
Céline Cudejko ◽  
Kristiaan Wouters ◽  
Lucía Fuentes ◽  
Sarah Anissa Hannou ◽  
Charlotte Paquet ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Macrophage Polarization ◽  
Suppressor Gene ◽  
In Vivo Model ◽  
Macrophage Phenotype ◽  
Age Related ◽  
Increased Risk ◽  
Increased Sensitivity

Abstract The CDKN2A locus, which contains the tumor suppressor gene p16INK4a, is associated with an increased risk of age-related inflammatory diseases, such as cardiovascular disease and type 2 diabetes, in which macrophages play a crucial role. Monocytes can polarize toward classically (CAMφ) or alternatively (AAMφ) activated macrophages. However, the molecular mechanisms underlying the acquisition of these phenotypes are not well defined. Here, we show that p16INK4a deficiency (p16−/−) modulates the macrophage phenotype. Transcriptome analysis revealed that p16−/− BM-derived macrophages (BMDMs) exhibit a phenotype resembling IL-4–induced macrophage polarization. In line with this observation, p16−/− BMDMs displayed a decreased response to classically polarizing IFNγ and LPS and an increased sensitivity to alternative polarization by IL-4. Furthermore, mice transplanted with p16−/− BM displayed higher hepatic AAMφ marker expression levels on Schistosoma mansoni infection, an in vivo model of AAMφ phenotype skewing. Surprisingly, p16−/− BMDMs did not display increased IL-4–induced STAT6 signaling, but decreased IFNγ-induced STAT1 and lipopolysaccharide (LPS)–induced IKKα,β phosphorylation. This decrease correlated with decreased JAK2 phosphorylation and with higher levels of inhibitory acetylation of STAT1 and IKKα,β. These findings identify p16INK4a as a modulator of macrophage activation and polarization via the JAK2-STAT1 pathway with possible roles in inflammatory diseases.

scholarly journals Metabolic biomarkers for peripheral artery disease compared with coronary artery disease: Lipoprotein and metabolite profiling of 31,657 individuals from five prospective cohorts

2020 ◽  
Author(s):  
Emmi Tikkanen ◽  
Vilma Jägerroos ◽  
Rodosthenis Rodosthenous ◽  
Michael Holmes ◽  
Naveed Sattar ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Peripheral Artery Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Vascular Diseases ◽  
Peripheral Artery ◽  
Ldl Particles ◽  
Increased Risk ◽  
Artery Disease

Background: Peripheral artery disease (PAD) and coronary artery disease (CAD) represent atherosclerosis in different vascular beds. We conducted detailed metabolic profiling to identify biomarkers for the risk of developing PAD and compared with risk of CAD to explore common and unique risk factors for these different vascular diseases. Methods: We measured blood biomarkers using nuclear magnetic resonance metabolomics in five Finnish prospective general-population cohorts (FINRISK 1997, 2002, 2007, 2012, and Health 2000 studies, n = 31,657). We used Cox modelling to estimate associations between biomarkers and incident symptomatic PAD and CAD (498 and 2073 events, respectively) during median follow-up time of 14 years. Results: The pattern of biomarker associations for incident PAD deviated from that for CAD. Apolipoproteins and cholesterol measures were robustly associated with incident CAD (for example, age- and sex-adjusted hazard ratio per SD for higher apolipoprotein B/A 1 ratio: 1.30; 95% confidence interval 1.25-1.36), but not with incident PAD (1.04; 0.95-1.14; Pheterogeneity < 0.001). Low-density lipoprotein (LDL) particle concentrations were also associated with incident CAD (e.g. small LDL particles: 1.24; 1.19-1.29) but not with PAD (1.07; 0.98-1.17; Pheterogeneity < 0.001). In contrast, more consistent associations of smaller LDL particle size and higher triglyceride levels in LDL and HDL particles with increased risk for both CAD and PAD events were seen (Pheterogeneity > 0.05). Many non-traditional biomarkers, including fatty acids, amino acids, inflammation- and glycolysis-related metabolites were associated with future PAD events. Lower levels of linoleic acid, an omega-6 fatty acid, and higher concentrations of glucose, lactate, pyruvate, glycerol and glycoprotein acetyls were more strongly associated with incident PAD as compared to CAD (Pheterogeneity < 0.001). The differences in metabolic biomarker associations for PAD and CAD remained when adjusting for body mass index, smoking, prevalent diabetes, and medications. Conclusions: The metabolic biomarker profile for future PAD risk is largely distinct from that of CAD. This may represent pathophysiological differences and may facilitate risk prediction.

Abstract 13080: Clinical Significance of Clonal Hematopoiesis With JAK2V617F in Patients With Cardiovascular Diseases

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kento Wada ◽  
Tomofumi Misaka ◽  
Tetsuro Yokokawa ◽  
Yusuke KIMISHIMA ◽  
Keiji Minakawa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Diseases ◽  
Multivariable Analysis ◽  
Myeloproliferative Neoplasm ◽  
Vascular Diseases ◽  
Interleukin 1Β ◽  
Clonal Hematopoiesis ◽  
Age Related ◽  
Artery Disease ◽  
Atherosclerotic Risk Factors

Background: It becomes increasingly clear that age-related clonal hematopoiesis (CH) is associated with cardiovascular diseases. However, CH with a driver mutation that causes myeloproliferative neoplasm (MPN) is not fully understood. Objective: To determine the clinical relevance of CH with MPN-driving mutations on cardiovascular diseases. Methods: This study prospectively enrolled 832 patients with cardiovascular diseases who did not show any hematological disorders. We examined the presence of the known MPN-driving mutations including JAK2V617F, CALRdel52, CALRins5, MPLW515L, and MPLW515K by an allele-specific polymerase chain reaction. Results: Out of 832 patients, 16 patients (1.9%) exhibited MPN-driving mutations including 15 patients with JAK2V617F (1.8%) and 1 patient with CALRins5 (0.1%). We divided the patients into two groups: vascular diseases including coronary artery disease, stroke, aortic aneurysm, aortic dissection, peripheral artery disease, deep vein thrombosis, and pulmonary thromboembolism (n=462, 55%) and non-vascular diseases (n=370, 45%). The prevalence of JAK2V617F-positive CH was significantly higher in patients with vascular diseases than in those with non-vascular diseases (2.8% vs. 0.5%, P = 0.014). In a multivariable analysis adjusted for known classic-atherosclerotic risk factors (age, male, obesity, smoking, hypertension, diabetes mellitus, dyslipidemia), the presence of JAK2V617F-positive CH was independently associated with vascular diseases (odds ratio, 5.448; P = 0.043). Additionally, peripheral leukocyte IL1B mRNA expressions as well as plasma interleukin-1β concentrations were significantly increased in patients with JAK2V617F-positive CH compared to those without JAK2V617F (P = 0.040 and P = 0.030, respectively). Conclusions: CH with JAK2V617F, but not CALR or MPL mutations, was significantly associated with vascular diseases independently on classic-atherosclerotic risk factors, in relation to interleukin-1β-related inflammatory mechanisms. JAK2V617F is a potential diagnostic and therapeutic target for vascular diseases.

Vascular Contributions to Brain Health: Cross-Cutting Themes

Stroke ◽  
2022 ◽  
Author(s):  
Steven M. Greenberg
Keyword(s):  
Successful Aging ◽  
Potential Role ◽  
Brain Health ◽  
Ethical Imperative ◽  
Small Vessels ◽  
Age Related ◽  
Brain Recovery ◽  
Recovery Mechanisms ◽  
Epidemiologic Risk ◽  
Pathophysiologic Mechanisms

As life expectancy grows, brain health is increasingly seen as central to what we mean by successful aging—and vascular brain health as central to overall brain health. Cerebrovascular pathologies are highly prevalent independent contributors to age-related cognitive impairment and at least partly modifiable with available treatments. The current Focused Update addresses vascular brain health from multiple angles, ranging from pathophysiologic mechanisms and neuroimaging features to epidemiologic risk factors, social determinants, and candidate treatments. Here we highlight some of the shared themes that cut across these distinct perspectives: 1) the lifetime course of vascular brain injury pathogenesis and progression; 2) the scientific and ethical imperative to extend vascular brain health research in non-White and non-affluent populations; 3) the need for improved tools to study the cerebral small vessels themselves; 4) the potential role for brain recovery mechanisms in determining vascular brain health and resilience; and 5) the cross-pathway mechanisms by which vascular and neurodegenerative processes may interact. The diverse perspectives featured in this Focused Update offer a sense of the multidisciplinary approaches and collaborations that will be required to launch our populations towards improved brain health and successful aging.

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