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atherosclerosis and senescence

Kuei-Chuan Chan, Meng-Hsun Yu, Ming-Cheng Lin, Chien-Ning Huang, Dai-Jung Chung, Yi-Ju Lee, Cheng-Hsun Wu, Chau-Jong Wang
Acarbose, an α-glucosidase inhibitor, is reported to reduce the incidence of silent myocardial infarction and slow the progression of intima-media thickening in patients with glucose intolerance. Here we investigate other impacts of acarbose on atherosclerosis development and the underlying mechanisms of atherosclerosis initiation and progression in vivo and in vitro. Rabbits fed a high cholesterol diet (HCD) were treated with acarbose (2.5-5.0 mg kg(-1)). Immunohistochemistry was used to assess the expression of inducible nitric oxide synthase (iNOS), Ras, proliferating cell nuclear antigen (PCNA), IL-6, β-galactosidase, and p-AMPK in atherosclerotic lesions...
December 7, 2016: Scientific Reports
Bennett G Childs, Darren J Baker, Tobias Wijshake, Cheryl A Conover, Judith Campisi, Jan M van Deursen
Advanced atherosclerotic lesions contain senescent cells, but the role of these cells in atherogenesis remains unclear. Using transgenic and pharmacological approaches to eliminate senescent cells in atherosclerosis-prone low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice, we show that these cells are detrimental throughout disease pathogenesis. We find that foamy macrophages with senescence markers accumulate in the subendothelial space at the onset of atherosclerosis, where they drive pathology by increasing expression of key atherogenic and inflammatory cytokines and chemokines...
October 28, 2016: Science
Mark R Schleiss
Congenital cytomegalovirus (CMV) infection is the most common infectious cause of disability in newborn infants. CMV also causes serious disease in solid organ (SOT) and haematopoietic stem cell transplant (HSCT) recipients. In otherwise healthy children and adults, primary CMV infection rarely causes illness. However, even asymptomatic CMV infections may predispose an individual towards an increased risk of atherosclerosis, cancer and immune senescence over the life course, although such associations remain controversial...
October 5, 2016: Journal of Virus Eradication
Jeong-Min Kim, Kwang-Yeol Park, Dong-Woo Shin, Moo-Seok Park, Oh-Sang Kwon
BACKGROUND AND AIMS: Elevated serum homocysteine level is known to be associated with increased risk of vascular event due to endothelial senescence. We investigated the association between serum homocysteine level and cerebral arteriosclerosis status including intracranial vascular calcification and atherosclerosis burden. METHODS: We identified 1193 consecutive patients (mean age = 68.6 ± 12.7, 537 female patients) who were admitted with acute cerebral infarction or transient ischemic attack from a single university medical center...
November 2016: Atherosclerosis
Munehiro Kitada, Yoshio Ogura, Daisuke Koya
Cardiovascular disease (CVD) due to atherosclerosis is the main cause of death in both the elderly and patients with metabolic diseases, including diabetes. Aging processes contribute to the pathogenesis of atherosclerosis. Calorie restriction (CR) is recognized as a dietary intervention for promoting longevity and delaying age-related diseases, including atherosclerosis. Sirt1, an NAD(+)-dependent deacetylase, is considered an anti-aging molecule and is induced during CR. Sirt1 deacetylates target proteins and is linked to cellular metabolism, the redox state and survival pathways...
October 15, 2016: Aging
Giuseppe Maltese, Paraskevi-Maria Psefteli, Benedetta Rizzo, Salil Srivastava, Luigi Gnudi, Giovanni E Mann, Richard C M Siow
Vascular ageing in conditions such as atherosclerosis, diabetes and chronic kidney disease, is associated with the activation of the renin angiotensin system (RAS) and diminished expression of antioxidant defences mediated by the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). The anti-ageing hormone klotho promotes longevity and protects against cardiovascular and renal diseases. Klotho has been shown to activate Nrf2 and attenuate oxidative damage in neuronal cells, however, the mechanisms by which it protects against vascular smooth muscle cell VSMC dysfunction elicited by Angiotensin II (AngII) remain to be elucidated...
October 3, 2016: Journal of Cellular and Molecular Medicine
Hyunyun Kim, Jisoo Yun, Sang-Mo Kwon
Accumulating evidence indicates that acute and chronic uncontrolled overproduction of oxidative stress-related factors including reactive oxygen species (ROS) causes cardiovascular diseases (CVDs), atherosclerosis, and diabetes. Moreover ROS mediate various signaling pathways underlying vascular inflammation in ischemic tissues. With respect to stem cell-based therapy, several studies clearly indicate that modulating antioxidant production at cellular levels enhances stem/progenitor cell functionalities, including proliferation, long-term survival in ischemic tissues, and complete differentiation of transplanted cells into mature vascular cells...
2016: Oxidative Medicine and Cellular Longevity
Kenneth Maiese
Circular ribonucleic acids (circRNAs) are non-coding RNAs of approximately 100 nucleotides in length with thousands of members in mammalian cells. The presence of circRNAs is believed to be even greater than that of messenger RNAs. Identification of circRNAs occurred approximately 37 years ago with the subsequent demonstration that covalent bonds are necessary for the unique circular structure of these ribonucleic acids. However, present understanding of the complex biological role of circRNAs remains limited and requires further elucidation...
2016: Journal of Translational Science
M G Pavlatou, A T Remaley, P W Gold
Klotho is a hormone secreted into human cerebrospinal fluid (CSF), plasma and urine that promotes longevity and influences the onset of several premature senescent phenotypes in mice and humans, including atherosclerosis, cardiovascular disease, stroke and osteoporosis. Preliminary studies also suggest that Klotho possesses tumor suppressor properties. Klotho's roles in these phenomena were first suggested by studies demonstrating that a defect in the Klotho gene in mice results in a significant decrease in lifespan...
August 30, 2016: Translational Psychiatry
Meili Wang, Yi Fu, Cheng Gao, Yiting Jia, Yaqian Huang, Limei Liu, Xian Wang, Wengong Wang, Wei Kong
Aging-related vascular dysfunction contributes to cardiovascular morbidity and mortality. Cartilage oligomeric matrix protein (COMP), a vascular extracellular matrix protein, has been described as a negative regulatory factor for the vascular aging-related processes including atherosclerosis and vascular calcification. However, whether COMP is implicated in the process of vascular aging remains unclear. Here, we identified a novel function of COMP in preventing vascular aging and vascular smooth muscle cells (VSMCs) senescence...
September 16, 2016: Biochemical and Biophysical Research Communications
Ya Gao, Juan Peng, Zhong Ren, Ni-Ya He, Qing Li, Xue-Shan Zhao, Mei-Mei Wang, Hong-Yan Wen, Zhi-Han Tang, Zhi-Sheng Jiang, Gui-Xue Wang, Lu-Shan Liu
MicroRNAs are a group of endogenously small non-coding RNA molecules that downregulate gene expression at the post-transcriptional level through binding to the 3'UTR of target mRNAs. Recent findings have revealed a key role for microRNAs in the pathophysiological processes of atherosclerosis. As a complex disease, atherosclerosis is influenced by a combination of multiple genes and environmental factors. Both of them play a role in atherogenesis by affecting different types of cells (such as endothelial cell, vascular smooth muscle cell and monocyte/macrophage) function...
September 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
Miguel López-Botet, Aura Muntasell, José E Martínez-Rodríguez, María López-Montañés, Marcel Costa-García, Aldi Pupuleku
Human cytomegalovirus (HCMV) establishes a highly prevalent life-long latent infection. Though generally subclinical, HCMV infection may have severe consequences during fetal development and in immunocompromised individuals. Based on epidemiological studies HCMV(+) serology has been associated with the development of atherosclerosis, immune senescence and an increase mortality rate in elderly people. Such long-term detrimental effects of the viral infection presumably result from an inefficient immune control of the pathogen, depending on the quality and evolution of the individual host-pathogen relationship...
September 2016: Mechanisms of Ageing and Development
Keizo Ohnaka
Dehydroepiandrosterone(DHEA), an adrenal androgen, has attracted much attention as an anti-aging hormone as well as a marker for senescence because of its unique change along with aging. DHEA is reported to have beneficial effects such as anti-diabetes, anti-obesity, and anti-atherosclerosis. It is also shown that DHEA has anti-osteoporosis effects to increase bone mineral density in randomized controlled trials(RCTs). As osteoblasts express aromatase which will convert androgen to estrogen, DHEA may act protectively against osteoporosis through its metabolites...
July 2016: Clinical Calcium
Abel Martin Garrido, Martin Bennett
PURPOSE OF REVIEW: Cell senescence is a major process regulating tissue mass, architecture and function, and underlies many diseases of ageing. Recent studies have elucidated some of the regulatory pathways leading to cell senescence, and senescence has also been found in the vasculature. However, assessment of cell senescence is problematic, and the effects of vascular cell senescence are in most cases unproven. The present article will review how senescence is assessed, how it is regulated, where senescence has been described, and the role of cell senescence in atherosclerosis...
October 2016: Current Opinion in Lipidology
Juan M Fernández-Alvira, Valentin Fuster, Beatriz Dorado, Nora Soberón, Ignacio Flores, Mercedes Gallardo, Stuart Pocock, María A Blasco, Vicente Andrés
BACKGROUND: Leucocyte telomere length (LTL) shortening is associated with cardiovascular ischemic events and mortality in humans, but data on its association with subclinical atherosclerosis are scarce. Whether the incidence and severity of subclinical atherosclerosis are associated with the abundance of critically short telomeres, a major trigger of cellular senescence, remains unknown. OBJECTIVES: The authors conducted a cross-sectional exploration of the association between subclinical atherosclerosis burden and both average LTL and the abundance of short telomeres (%LTL<3 kb)...
May 31, 2016: Journal of the American College of Cardiology
Mantas Matjusaitis, Greg Chin, Ethan Anders Sarnoski, Alexandra Stolzing
Aging is the main risk factor for many degenerative diseases and declining health. Senescent cells are part of the underlying mechanism for time-dependent tissue dysfunction. These cells can negatively affect neighbouring cells through an altered secretory phenotype: the senescence-associated secretory phenotype (SASP). The SASP induces senescence in healthy cells, promotes tumour formation and progression, and contributes to other age-related diseases such as atherosclerosis, immune-senescence and neurodegeneration...
August 2016: Ageing Research Reviews
Andreas Schober, Christian Weber
The maladaptation of endothelial cells to disturbed flow at arterial bifurcations increases permeability for lipoproteins. Additional injury by chemically modified lipoproteins disrupts the continuous repair of maladapted endothelial cells and triggers intimal macrophage accumulation. Macrophages remove modified lipoproteins from the extracellular space until the cholesterol overload leads to macrophage death and insufficient efferocytosis. This macrophage failure promotes the progression to advanced lesions by formation of a lipid-rich necrotic core, which may rupture and cause myocardial infarction and stroke...
May 23, 2016: Annual Review of Pathology
Paweł Żebrowski, Paweł Kulicki
Kidney diseases, with some exceptions, are diseases of the elderly. During last century mortality due to infections and injuries has gradually decreased and a longer life expectancy increased a rate of chronic diseases. Diabetes, hypertension and atherosclerosis have become most common causes of kidney diseases. A gradual nephrons loss in aging kidneys causes them more susceptible to acute injury as well as fastens the progression of their chronic disease. This leads to the rapid increase in the incidence of kidney diseases with aging...
2015: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
Yuri Hwang, Hee Tae Yu, Dong-Hyun Kim, Jiyeon Jang, Hee Young Kim, Insoo Kang, Hyeon Chang Kim, Sungha Park, Won-Woo Lee
BACKGROUND AND AIMS: The pathogenesis of coronary artery disease (CAD) is closely associated with chronic inflammatory processes. CD8(+) T cells are a key participant in the pathogenesis of atherosclerosis, the major cause of CAD; however, it remains unclear which CD8(+) T-cell subset is responsible. We investigated the immunological features of CD8(+) T cells expressing low and high levels of the IL-6 receptor α chain (IL-6Rα), a cytokine known to play a key role in cardiovascular diseases...
June 2016: Atherosclerosis
Hao Yin, J Geoffrey Pickering
Cellular senescence is a definable fate of cells within aging, diseased, and remodelling tissues. The traditional hallmark of cellular senescence is permanent cell cycle arrest but the senescent state is also accompanied by secretion of proteins that can reinforce the senescent phenotype and adversely affect the local tissue environment. Assessment for cellular markers of senescence has revealed the existence of senescent smooth muscle cells and senescent endothelial cells in vessels of patients with atherosclerosis and hypertension...
May 2016: Canadian Journal of Cardiology
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