Posts Tagged: risk factors

Long Noncoding RNA Discovery in Cardiovascular Disease: Decoding Form to Function

Long Noncoding RNA Discovery in Cardiovascular Disease: Decoding Form to Function

Tamer Sallam, Jaspreet Sandhu, Peter Tontonoz

Pipeline of long noncoding RNA (lncRNA) discovery and characterization. ASO indicates antisense oligonucleotide; ChiRP, chromatin isolation by RNA purification; qPCR, quantitative polymerase chain reaction; RAP, RNA antisense purification; and RIP, RNA immunoprecipitation. [Powerpoint File]

Somatic Mutations and Clonal Hematopoiesis: Unexpected Potential New Drivers of Age-Related Cardiovascular Disease

Somatic Mutations and Clonal Hematopoiesis: Unexpected Potential New Drivers of Age-Related Cardiovascular Disease

José J. Fuster, Kenneth Walsh

Somatic mutations in blood cells as a shared mechanism of hematologic cancer and cardiovascular disease. A, The accumulation of somatic mutations in hematopoietic progenitor and stem cells is an inevitable consequence of the process of aging. Some of these random mutations confer a competitive advantage to the mutant cells, leading to its clonal expansion. This phenomenon can be defined as somatic mutation-driven clonal hematopoiesis. B, Most individuals exhibiting somatic mutation-driven clonal hematopoiesis only carry 1 driver mutation (eg, in DNMT3A, TET2, ASXL1, or JAK2). Although this situation greatly increases the risk of acquiring additional driver mutations and eventually developing a hematologic cancer, this condition is infrequent, even in individuals with clonal hematopoiesis. The main cause of death in individuals exhibiting somatic mutation-driven clonal hematopoiesis is atherosclerotic cardiovascular disease. Grey shade in the figure indicates decreasing frequency. HSPC indicates hematopoietic stem/progenitor cell. [Powerpoint File]

Atrial Fibrillation Epidemiology, Pathophysiology, and Clinical Outcomes

Atrial Fibrillation: Epidemiology, Pathophysiology, and Clinical Outcomes

Laila Staerk, Jason A. Sherer, Darae Ko, Emelia J. Benjamin, Robert H. Helm

Atrial fibrillation (AF) risk factors (RFs) induce structural and histopathologic changes to the atrium that are characterized by fibrosis, inflammation, and cellular and molecular changes. Such changes increase susceptibility to AF. Persistent AF further induces electric and structural remodeling that promotes perpetuation of AF. AF also may lead to the development of additional AF risk factors that further alters the atrial substrate. Finally, AF is associated with several clinical outcomes. *There are limited data supporting the association. BMI, body mass index; ERP, effective refractory period; HF, heart failure; IL, interleukin; MI, myocardial infarction; OSA, obstructive sleep apnea; SEE, systemic embolism event; TNF, tumor necrosis factor; and VTE, venous thromboembolism. [Powerpoint File]

Neurodevelopmental Abnormalities and Congenital Heart Disease: Insights Into Altered Brain Maturation

Neurodevelopmental Abnormalities and Congenital Heart Disease: Insights Into Altered Brain Maturation

Paul D. Morton, Nobuyuki Ishibashi, Richard A. Jonas

A, Cortical gyrification increases throughout fetal and perinatal brain development. Legend demarks the 4 lobes of the cortex. B, Gyrification indices and (C) cortical surface areas of fetuses with hypoplastic left heart syndrome (HLHS) compared with normal fetuses. Adapted from Dubois and Dehaene-Lambertz (A)14 and Clouchoux et al (B and C)15 with permission of the publishers. Copyrights © 2015, 2013, Elsevier and Oxford University Press, respectively. Authorization for this adaptation has been obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation. [Powerpoint File]

Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke

Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke

Xiaoming Hu, T. Michael De Silva, Jun Chen, Frank M. Faraci

Structural alterations in endothelial cells are critical for blood–brain barrier (BBB) opening early after ischemic stroke. A, The opening of paracellular pathways: cytoskeletal rearrangements and related signaling in endothelial cells. B, The transcellular pathway of BBB leakage. ADF indicates actin-depolymerizing factor; CaM, calmodulin; LIMK, LIM kinase; MLC, myosin light chain; MLCK, MLC kinase; MLCP, MLC phosphatase; MMP, matrix metallopeptidase; ROCK: Rho kinase; TESK1, testicular protein kinase 1; and ZO, zonula occluden. [Powerpoint File]

Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke

Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke

Xiaoming Hu, T. Michael De Silva, Jun Chen, Frank M. Faraci

Pericytes play multifaceted roles in ischemia and reperfusion. Pericytes display both beneficial and detrimental functions during ischemia and reperfusion phases, and contribute significantly to the blood–brain barrier damage and repair. 1. Pericyte contraction and dilation regulate cerebral blood flow in the ischemic and perilesion areas. 2. Pericyte protects other neurovascular unit (NVU) components through releasing protective/trophic factors such as nerve growth factor (NGF), neurotrophin-3 (NT-3), vascular endothelial growth factor (VEGF), angiopoietin (Ang-1), and glial cell line-derived neurotrophic factor (GDNF). 3. Phagocytotic pericytes help to eliminate dead or injured tissue in the ischemic core, which in turn mitigates local inflammation and reduce secondary tissue damage. 4. Pericyte–endothelial cell interaction promotes angiogenesis after stroke. 5) Pericytes have the potential to serve as an origin of NVU components during tissue repair after ischemic stroke. Illustration credit: Ben Smith. [Powerpoint File]

Roles of Vascular Oxidative Stress and Nitric Oxide in the Pathogenesis of Atherosclerosis

Roles of Vascular Oxidative Stress and Nitric Oxide in the Pathogenesis of Atherosclerosis

Ulrich Förstermann, Ning Xia, Huige Li

Enzymes involved in the generation and inactivation of reactive oxygen species (ROS). Superoxide anion (O2·-) can be produced in the vascular wall by NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidases (Nox1 and Nox2), xanthine oxidase, uncoupled endothelial nitric oxide synthase (eNOS), and the mitochondrial respiration chain. O2·- can be converted to hydrogen peroxide (H2O2) by the enzyme superoxide dismutase (SOD). H2O2 can undergo spontaneous conversion to hydroxyl radical (OH·) via the Fenton reaction. OH· is extremely reactive and attacks most cellular components. H2O2 can be detoxified via glutathione (GSH) peroxidase, catalase or thioredoxin (Trx) peroxidase to H2O and O2. The enzyme myeloperoxidase can use H2O2 to oxidize chloride to the strong-oxidizing agent hypochlorous acid (HOCl). HOCl can chlorinate and thereby inactivate various biomolecules including lipoproteins and the eNOS substrate L-arginine. Besides HOCl generation, myelo-peroxidase can oxidize (and thus inactivate) NO to nitrite (NO2−) in the vasculature. Paraoxonase (PON) isoforms 2 and 3 can prevent mitochondrial O2·- generation. Reprinted from Li et al67 with permission of the publisher. Copyright © 2013, Elsevier. [Powerpoint File]

Stroke Caused by Atherosclerosis of the Major Intracranial Arteries

Stroke Caused by Atherosclerosis of the Major Intracranial Arteries

Chirantan Banerjee, Marc I. Chimowitz

Histological cross-section of intracranial atherosclerosis in basilar artery. Image courtesy Dr Tanya Turan. Red arrow—fibrous tissue, blue arrow—vessel wall, and green arrow—lipid [Powerpoint File]

Novel Risk Markers and Risk Assessments for Cardiovascular Disease

Novel Risk Markers and Risk Assessments for Cardiovascular Disease

Mark R. Thomas, Gregory Y.H. Lip

Acute coronary syndromes. A, Foam cells (derived from macrophages [Ma]) and lymphocytes have a central role in the development of a lipid-rich atherosclerotic plaque with a necrotic core (NC). Rupture or erosion of an atherosclerotic plaque triggers platelet (P) adhesion to subendothelial components, resulting in the formation of an occlusive thrombus, which also recruits monocytes (M) and neutrophils (N). Platelet–leukocyte interactions cause the release of proinflammatory cytokines and recruited neutrophils also release neutrophil extracellular traps. B, Myocardial ischemia, caused by coronary artery obstruction, leads to the recruitment of neutrophils and monocytes toward chemokines. Leukocyte adhesion molecules then mediate transmigration of leukocytes. Monocytes may then differentiate into Ma, alongside Ma that are already resident within myocardial tissue. Fibroblasts (F) proliferate and differentiate into myofibroblasts (MF). C, Impaired myocardial contractility and hemodynamics results in myocardial stretch, leading to consequent renal disturbances. [Powerpoint File]

Novel Risk Markers and Risk Assessments for Cardiovascular Disease

Novel Risk Markers and Risk Assessments for Cardiovascular Disease

Mark R. Thomas, Gregory Y.H. Lip

Heart failure. A, Myocardial injury, which may be triggered by a variety of insults, can lead to (B) myocardial necrosis, systemic inflammation, and infiltration of leukocytes, predominantly neutrophils (N), driven by chemokines and cytokines. N release their granule contents, thereby exerting oxidative stress and phagocytose necrotic cells and dead cardiomyocytes (DC) in conjunction with activated macrophages (Ma). C, A subsequent transition toward a reparative phase involves downregulation of the inflammatory response, release of anti-inflammatory cytokines, such as interleukin-10, and proliferation of monocytes (Mo) and lymphocytes (L). Fibroblasts (F) proliferate and differentiate in to myofibroblasts (MF), which promote collagen production and fibrosis, mediated in particular by transforming growth factor-β. D, The subsequent formation of a collagen (C)-rich scar maintains structural integrity of the myocardium at the expense of contractility and electric conductivity. [Powerpoint File]

Novel Risk Markers and Risk Assessments for Cardiovascular Disease

Novel Risk Markers and Risk Assessments for Cardiovascular Disease

Mark R. Thomas, Gregory Y.H. Lip

Atrial fibrillation (AF). The pathophysiology of AF is complex. Atrial fibrosis and electric abnormalities, including abnormal calcium homeostasis and ion-channel dysfunction, play a particularly prominent role in precipitating AF, whereas inflammation and oxidative stress reinforce pathological changes in myocardial structure. After the onset of AF, reduced blood flow through the atria predisposes toward thrombosis. The formation of an atrial thrombus, with subsequent embolization to the brain, is one of the most important causes of stroke, which may have devastating consequences. It is well-recognized that thrombosis may not purely be related to stasis of blood within the atria, but likely also reflects multiple clinical risk factors for stroke, which are particularly common in patients with AF. [Powerpoint File]

Cardiovascular Disease in Women: Clinical Perspectives

Cardiovascular Disease in Women: Clinical Perspectives

Mariana Garcia, Sharon L. Mulvagh, C. Noel Bairey Merz, Julie E. Buring, JoAnn E. Manson

Traditional and nontraditional atherosclerotic cardiovascular disease (ASCVD) risk factors in women. Increasing among women and more impactful traditional ASCVD risk factors include diabetes mellitus, hypertension, dyslipidemia, smoking, obesity, and physical inactivity. Emerging, nontraditional ASCVD risk factors include preterm delivery, hypertensive pregnancy disorders, gestational diabetes mellitus, breast cancer treatments, autoimmune diseases, and depression. [Powerpoint File]

 

Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease: New Insights From Epidemiology, Genetics, and Biology

Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease: New Insights From Epidemiology, Genetics, and Biology

Børge G. Nordestgaard

Suggested role of elevated plasma triglycerides and remnant cholesterol in the development of atherosclerosis including intimal low-grade inflammation through triglyceride hydrolysis and cholesterol accumulation in arterial wall foam cells. BMI indicates body mass index; FFA, free fatty acids; LDL, low-density lipoprotein; and LPL, lipoprotein lipase. Adapted from Nordestgaard and Varbo35 (with permission of the publisher; copyright ©2014, Elsevier) and Varbo et al.43 [Powerpoint File]

Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis

Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis

Michael A. Gimbrone Jr, Guillermo García-Cardeña

Endothelial-derived nitric oxide: production and biological actions. Endothelial cells rapidly produce nitric oxide (NO) via a unique isoform of NO synthase (eNOS) in response to agonists (eg, acetylcholine and bradykinin) and fluctuations in blood flow. Once generated, NO rapidly diffuses through the endothelial plasma membrane to activate guanylate cyclase in several cell types present in the blood (platelets and leukocytes) and also within the vessel wall (smooth muscle). Activation of guanylate cyclase in platelets results in inhibition of activation, adhesion, and aggregation; in leukocytes, decreased adhesivity; in smooth muscle cells, dephosphorylation of myosin light chain and vasorelaxation. NO also reacts with hemoglobin in erythrocytes, enhancing oxygen delivery to tissues. Chronic exposure of endothelial cells to laminar flow results in transcriptional upregulation of eNOS, thus increasing their NO-forming capacity (Illustration Credit: Ben Smith). [Powerpoint File]

Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis

Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis

Michael A. Gimbrone Jr, Guillermo García-Cardeña

Hemodynamics and endothelial phenotypes. Computational analyses of in vivo blood flow patterns in the carotid artery bifurcation, in normal human subjects, yielded representative near-wall shear stress waveforms from 2 hemodynamically distinct, clinically relevant locations: the distal internal carotid (an atherosclerosis-resistant region) and the carotid sinus (an atherosclerosis-susceptible region). Exposure of cultured human endothelial monolayers to these 2 distinct biomechanical stimuli, resulted in markedly different cell morphologies (visualized here by cytoskeletal actin staining) and functional phenotypes. Pulsatile (unidirectional) laminar flow induced upregulation of key transcription factors (Kruppel-like factor [KLF]-2, KLF4, and nuclear factor erythroid 2-related factor [Nrf]-2), which orchestrated a multifunctional atheroprotective phenotype; in contrast, disturbed (oscillatory) flow resulted in enhanced expression of the pleiotropic transcription factor NF-κB, resulting in a proinflammatory, atheroprone phenotype.161 [Powerpoint File]