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Pathogenesis and pathophysiology of Atherosclerosis

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372 papers 25 to 100 followers Theory and research into the molecular causes and hemodynamics consequences of the atherosclerotic lesion
By Gregory Gustafson Interventional Cardiologist
https://www.readbyqxmd.com/read/29627296/relationship-between-lipoprotein-subfraction-cholesterol-and-residual-risk-for-cardiovascular-outcomes-a-post-hoc-analysis-of-the-aim-high-trial
#1
Peter P Toth, Steven R Jones, April Slee, Jerome Fleg, Santica M Marcovina, Megan Lacy, Ruth McBride, William E Boden
BACKGROUND: The AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes) trial failed to demonstrate incremental clinical benefit of extended-release niacin (ERN) in 3414 statin-treated patients with established cardiovascular (CV) disease who had low baseline levels of high-density lipoprotein cholesterol (HDL-C) as compared to placebo. A previous secondary analysis suggested that ERN provided outcome benefits in ERN-treated patients with high triglycerides (TGs; >200 mg/dL) and very low HDL-C (<32 mg/dL) at baseline...
March 9, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29588315/cholesterol-efflux-pathways-suppress-inflammasome-activation-netosis-and-atherogenesis
#2
Marit Westerterp, Panagiotis Fotakis, Mireille Ouimet, Andrea E Bochem, Hanrui Zhang, Matthew M Molusky, Wei Wang, Sandra Abramowicz, Sacha la Bastide-van Gemert, Nan Wang, Carrie L Welch, Muredach P Reilly, Erik S Stroes, Kathryn J Moore, Alan R Tall
Background -The CANTOS trial showed that antagonism of interleukin-1β (IL-1β) reduces coronary heart disease in patients with a previous myocardial infarction and evidence of systemic inflammation, indicating that pathways required for IL-1β secretion increase cardiovascular risk. IL-1β and IL-18 secretion are produced via the NLRP3 inflammasome in myeloid cells in response to cholesterol accumulation, but mechanisms linking NLRP3 inflammasome activation to atherogenesis are unclear. The cholesterol transporters ATP Binding Cassette A1 and G1 (ABCA1/G1) mediate cholesterol efflux to high-density-lipoprotein (HDL) and Abca1/g1 deficiency in myeloid cells leads to cholesterol accumulation...
March 27, 2018: Circulation
https://www.readbyqxmd.com/read/29589525/impact-of-dysfunctional-protein-catabolism-on-macrophage-cholesterol-handling
#3
Takuro Miyazaki, Akira Miyazaki
Protein catabolism in macrophages, which is accomplished mainly through autophagy-lysosomal degradation, ubiquitin-proteasome system, and calpains, is disturbed in atheroprone vessels. Moreover, growing evidence suggests that defects in protein catabolism interfere with cholesterol handling in macrophages. Indeed, decreases in autophagy facilitate the deposition of cholesterol in atheroprone macrophages and the subsequent development of vulnerable atherosclerotic plaques due to impaired catabolism of lipid droplets and limited efferocytic clearance of deadly cells...
March 26, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29593789/drugs-involved-in-dyslipidemia-and-obesity-treatment-focus-on-adipose-tissue
#4
REVIEW
Sofia Dias, Sílvia Paredes, Laura Ribeiro
Metabolic syndrome can be defined as a state of disturbed metabolic homeostasis characterized by visceral obesity, atherogenic dyslipidemia, arterial hypertension, and insulin resistance. The growing prevalence of metabolic syndrome will certainly contribute to the burden of cardiovascular disease. Obesity and dyslipidemia are main features of metabolic syndrome, and both can present with adipose tissue dysfunction, involved in the pathogenic mechanisms underlying this syndrome. We revised the effects, and underlying mechanisms, of the current approved drugs for dyslipidemia and obesity (fibrates, statins, niacin, resins, ezetimibe, and orlistat; sibutramine; and diethylpropion, phentermine/topiramate, bupropion and naltrexone, and liraglutide) on adipose tissue...
2018: International Journal of Endocrinology
https://www.readbyqxmd.com/read/29600751/electronegative-ldl-an-active-player-in-atherogenesis-or-a-by-product-of-atherosclerosis
#5
Andrea Rivas-Urbina, Anna Rull, Jordi Ordonez-Llanos, Jose Luis Sanchez-Quesada
Low-density lipoproteins (LDLs) are the major plasma carriers of cholesterol. However, LDL particles must undergo various molecular modifications to promote the development of atherosclerotic lesions. Modified LDL can be generated by different mechanisms, but as a common trait, show an increased electronegative charge of the LDL particle. A subfraction of LDL with increased electronegative charge (LDL(-)), which can be isolated from blood, exhibits several pro-atherogenic characteristics. LDL(-) is heterogeneous, due to its multiple origins but is strongly related to the development of atherosclerosis...
March 29, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29601312/myeloid-cells-regulate-plasma-ldl-cholesterol-levels
#6
Venetia Bazioti, Anouk M La Rose, Marit Westerterp
PURPOSE OF REVIEW: Leukocytosis, elevated blood leukocyte levels, is associated with enhanced cardiovascular risk in humans. Hematopoietic stem and progenitor cells (HSPCs) drive leukocyte production in a process called hematopoiesis, which mainly occurs in the bone marrow, and under certain conditions also in other organs such as the spleen. Cholesterol accumulation in HSPCs enhances hematopoiesis, increasing levels of blood monocytes that infiltrate into atherosclerotic plaques. Although HSPC proliferation and monocytosis enhance atherogenesis in several studies, concomitant decreases in LDL-cholesterol levels have also been reported, associated with anti-atherogenic effects...
March 29, 2018: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/29617722/pcsk9-regulates-expression-of-scavenger-receptors-and-ox-ldl-uptake-in-macrophages
#7
Zufeng Ding, Shijie Liu, Xianwei Wang, Sue Theus, Xiaoyan Deng, Yubo Fan, Sichang Zhou, Jawahar L Mehta
Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to influence macrophage biology and modulate atherogenesis. We conducted this study to examine the regulation of scavenger receptors (SRs) (LOX-1, SRA, and CD36) and oxidized liporoptein cholesterol (ox-LDL) uptake in macrophages by PCSK9. Methods and results: Treatment of mouse peritoneal macrophages with tumour necrosis factor alpha (TNF-α) resulted in concentration-dependent modest, but significant, increase in PCSK9 expression...
March 29, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29359673/non-traditional-cardiovascular-risk-markers-in-the-era-of-established-major-risk-factors-and-multiple-guidelines
#8
Thomas F Whayne
The non-traditional cardiovascular (CV) risk factors that appear to be of most clinical interest include: apolipoprotein A (ApoA), apolipoprotein B (ApoB), high-sensitivity C-Reactive protein (hsCRP), homocysteine, interleukin 1 (IL1), lipoprotein (a) [Lp(a)], the density of low-density lipoprotein (LDL) particles, the LDL particle number, tissue/tumor necrosis factor-α (TNF-α) and uric acid. These non-traditional risk factors may be of value in adding further confirmation and attention to suspected significant CV risk...
January 22, 2018: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/29360955/vascular-smooth-muscle-cell-death-autophagy-and-senescence-in-atherosclerosis
#9
Mandy O J Grootaert, Manon Moulis, Lynn Roth, Wim Martinet, Cécile Vindis, Martin R Bennett, Guido R Y De Meyer
In the present review, we describe the causes and consequences of loss of vascular smooth muscle cells (VSMCs) or their function in advanced atherosclerotic plaques and discuss possible mechanisms such as cell death or senescence, and induction of autophagy to promote cell survival. We also highlight the potential use of pharmacological modulators of these processes to limit plaque progression and/or improve plaque stability. VSMCs play a pivotal role in atherogenesis. Loss of VSMCs via initiation of cell death leads to fibrous cap thinning and promotes necrotic core formation and calcification...
March 15, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29370236/ethyl-pyruvate-inhibits-oxidation-of-ldl-in-vitro-and-attenuates-oxldl-toxicity-in-ea-hy926-cells
#10
Christine Rossmann, Christoph Nusshold, Margret Paar, Gerhard Ledinski, Erwin Tafeit, Martin Koestenberger, Eva Maria Bernhart, Wolfgang Sattler, Gerhard Cvirn, Seth Hallström
BACKGROUND: Ethyl pyruvate (EP) exerts anti-inflammatory and anti-oxidative properties. The aim of our study was to investigate whether EP is capable of inhibiting the oxidation of LDL, a crucial step in atherogenesis. Additionally, we examined whether EP attenuates the cytotoxic effects of highly oxidized LDL in the human vascular endothelial cell line EA.hy926. METHODS: Native LDL (nLDL) was oxidized using Cu2+ ions in the presence of increasing amounts of EP...
2018: PloS One
https://www.readbyqxmd.com/read/29384050/polyphenols-potential-use-in-the-prevention-and-treatment-of-cardiovascular-diseases
#11
Rosaria Vincenza Giglio, Angelo Maria Patti, Arrigo F G Cicero, Giuseppe Lippi, Manfredi Rizzo, Peter P Toth, Maciej Banach
BACKGROUND: Polyphenols are bioactive compounds that can be found mostly in foods like fruits, cereals, vegetables, dry legumes, chocolate and beverages such as coffee, tea and wine. They are extensively used in the prevention and treatment of cardiovascular disease (CVD) providing protection against many chronic illnesses. Their effects on human health depend on the amount consumed and on their bioavailability. Many studies have demonstrated that polyphenols have also good effects on the vascular system by lowering blood pressure, improving endothelial function, increasing antioxidant defences, inhibiting platelet aggregation and low-density lipoprotein oxidation, and reducing inflammatory responses...
2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29393413/suppressive-effects-of-berberine-on-atherosclerosis-via-downregulating-visfatin-expression-and-attenuating-visfatin-induced-endothelial-dysfunction
#12
Qiang Wan, Zhongyong Liu, Yuping Yang, Xiaobing Cui
Berberine (BBR) possesses significant anti-atherosclerosis properties. Visfatin is one of the most promising biomarkers of incoming atherosclerosis. However, research on the effect of BBR on regulating visfatin expression in atherogenesis remains largely unknown. In this study, we investigated the effects of BBR on visfatin expression and atherogenesis in apolipoprotein E knockout (ApoE-/-) mice. The effect of BBR on attenuating visfatin-induced endothelial dysfunction was also evaluated in cultured human umbilical vein endothelial cells (HUVECs)...
April 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29393918/nanotherapeutics-containing-lithocholic-acid-based-amphiphilic-scorpion-like-macromolecules-reduce-in-vitro-inflammation-in-macrophages-implications-for-atherosclerosis
#13
Alysha Moretti, Qi Li, Rebecca Chmielowski, Laurie B Joseph, Prabhas V Moghe, Kathryn E Uhrich
Previously-designed amphiphilic scorpion-like macromolecule (AScM) nanoparticles (NPs) showed elevated potency to counteract oxidized low-density lipoprotein (oxLDL) uptake in atherosclerotic macrophages, but failed to ameliorate oxLDL-induced inflammation. We designed a new class of composite AScMs incorporating lithocholic acid (LCA), a natural agonist for the TGR5 receptor that is known to counteract atherosclerotic inflammation, with two complementary goals: to simultaneously decrease lipid uptake and inhibit pro-inflammatory cytokine secretion by macrophages...
February 2, 2018: Nanomaterials
https://www.readbyqxmd.com/read/29396513/pcsk9-induces-a-pro-inflammatory-response-in-macrophages
#14
Chiara Ricci, Massimiliano Ruscica, Marina Camera, Laura Rossetti, Chiara Macchi, Alessandra Colciago, Ilaria Zanotti, Maria Giovanna Lupo, Maria Pia Adorni, Arrigo F G Cicero, Federica Fogacci, Alberto Corsini, Nicola Ferri
Intraplaque release of inflammatory cytokines from macrophages is implicated in atherogenesis by inducing the proliferation and migration of media smooth muscle cells (SMCs). PCSK9 is present and released by SMCs within the atherosclerotic plaque but its function is still unknown. In the present study, we tested the hypothesis that PCSK9 could elicit a pro-inflammatory effect on macrophages. THP-1-derived macrophages and human primary macrophages were exposed to different concentrations (0.250 ÷ 2.5 µg/ml) of human recombinant PCSK9 (hPCSK9)...
February 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29407889/microrna-24-aggravates-atherosclerosis-by-inhibiting-selective-lipid-uptake-from-hdl-cholesterol-via-the-post-transcriptional-repression-of-scavenger-receptor-class-b-type-i
#15
Kun Ren, Xiao Zhu, Zhi Zheng, Zhong-Cheng Mo, Xiao-Shan Peng, Yong-Zhi Zeng, Han-Xiao Ou, Qing-Hai Zhang, Hui-Zhou Qi, Guo-Jun Zhao, Guang-Hui Yi
BACKGROUND AND AIMS: Liver scavenger receptor class B type I (SR-BI) exerts atheroprotective effects through selective lipid uptake (SLU) from high-density lipoprotein cholesterol (HDL-C). Low hepatic SR-BI expression leads to high HDL-C levels in the circulation and an increased risk of atherosclerosis. Furthermore, macrophage SR-BI mediates bidirectional cholesterol flux and may protect against atherogenesis. Previous studies have revealed that miR-24 is closely related to cardiovascular disease (CVD) progression...
March 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29031990/international-standardization-of-diagnostic-criteria-for-microvascular-angina
#16
Peter Ong, Paolo G Camici, John F Beltrame, Filippo Crea, Hiroaki Shimokawa, Udo Sechtem, Juan Carlos Kaski, C Noel Bairey Merz
Standardization of diagnostic criteria for ischemic symptoms due to coronary microvascular dysfunction (CMD) is needed for further investigation of patients presenting with anginal chest pain consistent with "microvascular angina" (MVA). At the annual Coronary Vasomotion Disorders International Study Group (COVADIS) Summits held in August 2014 and 2015, the following criteria were agreed upon for the investigative diagnosis of microvascular angina: (1) presence of symptoms suggestive of myocardial ischemia; (2) objective documentation of myocardial ischemia, as assessed by currently available techniques; (3) absence of obstructive CAD (<50% coronary diameter reduction and/or fractional flow reserve (FFR) >0...
January 1, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/28916255/impact-of-nonfasting-triglycerides-high-density-lipoprotein-cholesterol-ratio-on-secondary-prevention-in-patients-treated-with-statins
#17
Ichiro Matsumoto, Atsushi Misaki, Mizuki Kurozumi, Tsunetatsu Nanba, Yuichiro Takagi
BACKGROUND: Some studies have demonstrated that low-density lipoprotein cholesterol (LDL-C) lowering therapy is one of the most important strategies to prevent coronary artery disease. Also, serum triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) are recognized as independent risk factors of cardiovascular diseases. The aim of this study was to investigate whether the nonfasting TG/HDL-C ratio could affect the incidence of cardiovascular events after percutaneous coronary intervention (PCI) even in patients treated with statins...
January 2018: Journal of Cardiology
https://www.readbyqxmd.com/read/28916641/inflammation-and-atherosclerosis-the-end-of-a-controversy
#18
Göran K Hansson
No abstract text is available yet for this article.
November 14, 2017: Circulation
https://www.readbyqxmd.com/read/28538136/genetic-and-pharmacologic-inactivation-of-angptl3-and-cardiovascular-disease
#19
RANDOMIZED CONTROLLED TRIAL
Frederick E Dewey, Viktoria Gusarova, Richard L Dunbar, Colm O'Dushlaine, Claudia Schurmann, Omri Gottesman, Shane McCarthy, Cristopher V Van Hout, Shannon Bruse, Hayes M Dansky, Joseph B Leader, Michael F Murray, Marylyn D Ritchie, H Lester Kirchner, Lukas Habegger, Alex Lopez, John Penn, An Zhao, Weiping Shao, Neil Stahl, Andrew J Murphy, Sara Hamon, Aurelie Bouzelmat, Rick Zhang, Brad Shumel, Robert Pordy, Daniel Gipe, Gary A Herman, Wayne H H Sheu, I-Te Lee, Kae-Woei Liang, Xiuqing Guo, Jerome I Rotter, Yii-Der I Chen, William E Kraus, Svati H Shah, Scott Damrauer, Aeron Small, Daniel J Rader, Anders Berg Wulff, Børge G Nordestgaard, Anne Tybjærg-Hansen, Anita M van den Hoek, Hans M G Princen, David H Ledbetter, David J Carey, John D Overton, Jeffrey G Reid, William J Sasiela, Poulabi Banerjee, Alan R Shuldiner, Ingrid B Borecki, Tanya M Teslovich, George D Yancopoulos, Scott J Mellis, Jesper Gromada, Aris Baras
BACKGROUND: Loss-of-function variants in the angiopoietin-like 3 gene (ANGPTL3) have been associated with decreased plasma levels of triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. It is not known whether such variants or therapeutic antagonism of ANGPTL3 are associated with a reduced risk of atherosclerotic cardiovascular disease. METHODS: We sequenced the exons of ANGPTL3 in 58,335 participants in the DiscovEHR human genetics study...
July 20, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28482008/the-microcirculation-a-key-player-in-obesity-associated-cardiovascular-disease
#20
Oana Sorop, T Dylan Olver, Jens van de Wouw, Ilkka Heinonen, Richard W van Duin, Dirk J Duncker, Daphne Merkus
It is increasingly recognized that obesity is a risk factor for microvascular disease, involving both structural and functional changes in the microvasculature. This review aims to describe how obesity impacts the microvasculature of a variety of tissues, including visceral adipose tissue, skeletal muscle, heart, brain, kidneys, and lungs. These changes involve endothelial dysfunction, which in turn (i) impacts control of vascular tone, (ii) contributes to development of microvascular insulin resistance, (iii) alters secretion of paracrine factors like nitric oxide and endothelin, but (iv) also influences vascular structure and perivascular inflammation...
July 1, 2017: Cardiovascular Research
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