Posts Tagged: biomarkers

Extracellular Vesicles in Cardiovascular Disease: Potential Applications in Diagnosis, Prognosis, and Epidemiology

Extracellular Vesicles in Cardiovascular Disease: Potential Applications in Diagnosis, Prognosis, and Epidemiology

Felix Jansen, Georg Nickenig, Nikos Werner

Extracellular vesicles (EVs) as biomarker in different stages of coronary artery disease. Levels of circulating EVs are detectable in plasma of healthy subjects and are elevated in patients with cardiovascular risk factors or already present cardiovascular diseases. This figure summarizes EV surface markers from clinical studies, which showed increased circulating levels of endothelial-, platelet-, white blood cell–, and red blood cell–derived EVs in different stages of coronary artery disease from patients at risk to acute coronary syndromes (Illustration credit: Ben Smith). [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

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]

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]

Circulating Noncoding RNAs as Biomarkers of Cardiovascular Disease and Injury

Circulating Noncoding RNAs as Biomarkers of Cardiovascular Disease and Injury

Janika Viereck, Thomas Thum

Biogenesis and function of microRNAs (miRNAs). MiRNAs are transcribed from longer precursors with protein or other noncoding gene sequences and further processed via 2 endonucleolytic processing steps. Mature miRNAs associate with Argonaute proteins (Ago2) forming the RNA-induced silencing complex (miRISC). Within this complex, miRNAs recognize their target sequence and block their expression by translational repression or degradation. MiRNAs can be released or actively secreted into the extracellular space and circulatory system stabilized in vesicles or proteinous binding partners. DGCR8, DiGeorge syndrome critical region 8; TRBP, transactivation-responsive RNA-binding protein. [Powerpoint File]

Circulating Noncoding RNAs as Biomarkers of Cardiovascular Disease and Injury

Circulating Noncoding RNAs as Biomarkers of Cardiovascular Disease and Injury

Janika Viereck, Thomas Thum

Molecular mechanism of long noncoding RNA (lncRNA) activities. LncRNAs regulate the expression of genes in the nucleus by interacting directly with DNA recruiting chromatin modifying complexes and various transcriptional regulators. Cytoplasmatic noncoding transcripts act as sponges for other transcripts like microRNAs (miRNAs) or for proteins, serve as templates for small peptide synthesis or regulate messenger RNA (mRNA) degradation and translation. These transcripts enter the bloodstream bound to proteinous carriers or incorporated into extracellular vesicles that leads to a stabilization of transcripts. Ago2, Argonaute protein 2. [Powerpoint File]

Circulating MicroRNAs: Novel Biomarkers and Extracellular Communicators in Cardiovascular Disease?

Circulating MicroRNAs: Novel Biomarkers and Extracellular Communicators in Cardiovascular Disease?

Esther E. Creemers, Anke J. Tijsen, Yigal M. Pinto

Cellular release mechanisms and extracellular transportation systems of miRNAs. In the nucleus, miRNAs are transcribed from DNA. A precursor hairpin miRNA (pre-miRNA) is formed after cleavage by the RNase III enzyme Drosha. After being transported into the cytoplasm, the pre-miRNA can be further cleaved into 19- to 23-nucleotide mature miRNA duplexes. One strand of the miRNA duplex can be loaded into the RNA-induced silencing complex (RISC), where it can guide the RISC to specific mRNA targets to prevent translation of the mRNA into protein (1). The other strand may be degraded or released from the cell through export mechanisms described below. In the cytoplasm, pre-miRNAs can also be incorporated into small vesicles called exosomes, which originate from the endosome and are released from cells when multivesicular bodies (MVB) fuse with the plasma membrane (2). Cytoplasmic miRNAs (pre-miRNA or mature miRNA) can also be released by microvesicles, which are released from the cell through blebbing of the plasma membrane (3). miRNAs are also found in circulation in microparticle-free form. These miRNAs can be associated with high-density lipoproteins or bound to RNA-binding proteins such as Ago2. It is not known how these miRNA-protein complexes are released from the cell. These miRNAs may be released passively, as by-products of dead cells, or actively, in an miRNA-specific manner, through interaction with specific membrane channels or proteins (4). Although pre-miRNAs have been detected in exosomes and microvesicles,20 and mature miRNAs have been found in complex with Ago28 and HDL,9 the exact proportion of mature and pre-miRNAs in the different extracellular compartments is not known. Illustration credit: Cosmocyte/Ben Smith. [Powerpoint File]

Assessing Cell and Organ Senescence Biomarkers

Assessing Cell and Organ Senescence Biomarkers

Bruno Bernardes de Jesus, Maria A. Blasco

Telomeres structure and senescence. Telomeres form a protective structure (T-loop) that is covered by a complex of different proteins named shelterin (and other proteins not detailed here12). Telomere shortening and uncapping are believed to result in senescence.210 Although telomere shortening involves uncapping, it was observed that uncapping per se could result in a senescent condition without modifications in the telomere length.35,211 Short telomeres or telomeres that lost the aptitude to form the T-loops could lead to the activation of DNA damage response (DDR) and trigger senescence.12,29 [Powerpoint File]