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Pathogenesis and pathophysiology of Atherosclerosis

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382 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/29713054/structures-of-angptl3-and-angptl4-modulators-of-triglyceride-levels-and-coronary-artery-disease
#1
Ekaterina Biterova, Mariam Esmaeeli, Heli I Alanen, Mirva Saaranen, Lloyd W Ruddock
Coronary artery disease is the most common cause of death globally and is linked to a number of risk factors including serum low density lipoprotein, high density lipoprotein, triglycerides and lipoprotein(a). Recently two proteins, angiopoietin-like protein 3 and 4, have emerged from genetic studies as being factors that significantly modulate plasma triglyceride levels and coronary artery disease. The exact function and mechanism of action of both proteins remains to be elucidated, however, mutations in these proteins results in up to 34% reduction in coronary artery disease and inhibition of function results in reduced plasma triglyceride levels...
April 30, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29801689/mendelian-randomization-its-impact-on-cardiovascular-disease
#2
REVIEW
Masa-Aki Kawashiri, Hayato Tada, Akihiro Nomura, Masakazu Yamagishi
Cardiovascular diseases and their risk factors are inheritable. Single nucleotide polymorphisms in the human genome are found in around 1 in 1000 base pairs, and this may affect the genetic variety of individuals. During meiosis, any genetic information is randomized and is independent of other characteristics. In a Mendelian randomization study (MRS), a genetic variant associated with biomarker is used as a proxy for the biomarker, and the outcomes are compared between the groups harboring the effect alleles and a group with the reference allele...
May 22, 2018: Journal of Cardiology
https://www.readbyqxmd.com/read/29875140/validity-of-inducible-ischaemia-as-a-surrogate-for-adverse-outcomes-in-stable-coronary-artery-disease
#3
Adam Timmis, Antony Raharja, R Andrew Archbold, Anthony Mathur
Regional myocardial ischaemia is commonly expressed as exertional angina in patients with stable coronary artery disease (CAD). It also associates with prognosis, risk tending to increase with the severity of ischaemia. The validity of myocardial ischaemia as a surrogate for adverse clinical outcomes, however, has not been well established. Thus, in cohort studies, ischaemia testing has failed to influence rates of myocardial infarction and coronary death. Moreover, in clinical studies, pharmacological and interventional treatments that are effective in correcting ischaemia have rarely been shown to reduce cardiovascular (CV) risk...
June 6, 2018: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/29703625/elevated-lipoprotein-a-and-low-density-lipoprotein-cholesterol-as-predictors-of-the-severity-and-complexity-of-angiographic-lesions-in-patients-with-premature-coronary-artery-disease
#4
David Chieng, Jing Pang, Katrina L Ellis, Graham S Hillis, Gerald F Watts, Carl J Schultz
BACKGROUND: Elevated lipoprotein(a) (Lp[a]) and low-density lipoprotein (LDL) cholesterol are important inheritable risk factors for premature coronary artery disease (CAD). Lp(a) mediates cardiovascular risk through prothrombotic, proinflammatory, and proatherogenic properties. The association of Lp(a) and LDL cholesterol with angiographic disease severity and complexity in patients with premature CAD has yet to be established. OBJECTIVE: To investigate the relationship of Lp(a) and LDL cholesterol with the severity and complexity of coronary artery lesions using the SYNergy between percutaneous coronary intervention with TAXUS and Cardiac Surgery (SYNTAX) and Gensini scores, in patients with premature CAD...
April 3, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29858423/plasma-concentrations-of-molecular-lipid-species-predict-long-term-clinical-outcome-in-coronary-artery-disease-patients
#5
Sharda S Anroedh, Mika Hilvo, K Martijn Akkerhuis, Dimple Kauhanen, Kaisa Koistinen, Rohit Oemrawsingh, Patrick Serruys, Robert-Jan van Geuns, Eric Boersma, Reijo Laaksonen, Isabella Kardys
PURPOSE: We investigated the associations of ten previously identified high risk molecular lipid species and three ceramide ratios with the occurrence of major adverse cardiac events (MACE) during a median follow-up of 4.7 years in patients with coronary artery disease (CAD). METHODS: Between 2008 and 2011, 581 patients underwent diagnostic coronary angiography or percutaneous coronary intervention for stable angina pectoris (SAP) or acute coronary syndrome (ACS)...
June 1, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29888618/association-between-elevated-plasma-microrna-223-content-and-severity-of-coronary-heart-disease
#6
Ji-Fang Guo, Yu Zhang, Qing-Xia Zheng, Yao Zhang, Hui-Hua Zhou, Lun-Meng Cui
Bioinformatics indicate that miR-223 regulates many genes associated with cholesterol metabolism, and it could also control high-density lipoprotein-cholesterol (HDL-C) uptake. As reported in previous study, miR-223 was found to be upregulated from human subjects with familial hypercholesterolaemia, however, it remains to be determined using a larger group of coronary heart disease (CHD) patients. Moreover, whether it correlates with severity of atherogenesis, has never been elucidated before. We aim to further explore the association between circulating miR-223 content and severity of CHD...
June 10, 2018: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/29785308/the-correlation-of-dyslipidemia-with-the-extent-of-coronary-artery-disease-in-the-multiethnic-study-of-atherosclerosis
#7
Moshrik Abd Alamir, Michael Goyfman, Adib Chaus, Firas Dabbous, Leslie Tamura, Veit Sandfort, Alan Brown, Mathew Budoff
Background: The extent of coronary artery calcium (CAC) improves cardiovascular disease (CVD) risk prediction. The association between common dyslipidemias (combined hyperlipidemia, simple hypercholesterolemia, metabolic Syndrome (MetS), isolated low high-density lipoprotein cholesterol, and isolated hypertriglyceridemia) compared with normolipidemia and the risk of multivessel CAC is underinvestigated. Objectives: To determine whether there is an association between common dyslipidemias compared with normolipidemia, and the extent of coronary artery involvement among MESA participants who were free of clinical cardiovascular disease at baseline...
2018: Journal of Lipids
https://www.readbyqxmd.com/read/29688308/visit-to-visit-cholesterol-variability-correlates-with-coronary-atheroma-progression-and-clinical-outcomes
#8
Donald Clark, Stephen J Nicholls, Julie St John, Mohamed B Elshazly, Samir R Kapadia, E Murat Tuzcu, Steven E Nissen, Rishi Puri
Aims: Utilizing serial intravascular ultrasonography (IVUS), we aimed to exam the association of intra-individual lipid variability, coronary atheroma progression, and clinical outcomes. Methods and results: We performed a post hoc patient-level analysis of nine clinical trials involving 4976 patients with coronary artery disease who underwent serial coronary IVUS in the setting of a range of medical therapies. We assessed the associations between progression in percent atheroma volume (ΔPAV), clinical outcomes, and visit-to-visit lipid variability including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC)/HDL-C, and apolipoprotein B (ApoB)...
April 21, 2018: European Heart Journal
https://www.readbyqxmd.com/read/29212778/identification-of-64-novel-genetic-loci-provides-an-expanded-view-on-the-genetic-architecture-of-coronary-artery-disease
#9
Pim van der Harst, Niek Verweij
RATIONALE: Coronary artery disease (CAD) is a complex phenotype driven by genetic and environmental factors. Ninety-seven genetic risk loci have been identified to date, but the identification of additional susceptibility loci might be important to enhance our understanding of the genetic architecture of CAD. OBJECTIVE: To expand the number of genome-wide significant loci, catalog functional insights, and enhance our understanding of the genetic architecture of CAD...
February 2, 2018: Circulation Research
https://www.readbyqxmd.com/read/29618599/triglyceride-rich-lipoprotein-cholesterol-and-risk-of-cardiovascular-events-among-patients-receiving-statin-therapy-in-the-treating-to-new-targets-tnt-trial
#10
Antonio J Vallejo-Vaz, Rana Fayyad, S Matthijs Boekholdt, G Kees Hovingh, John J Kastelein, Shari Melamed, Philip Barter, David D Waters, Kausik K Ray
Background -Mendelian randomization data suggest genetic determinants of lifetime higher triglyceride-rich lipoprotein-cholesterol (TRL-C) are causally related to cardiovascular disease and therefore a potential therapeutic target. The relevance of TRL-C among patients receiving statins is unknown. We assessed the relationship between TRL-C and cardiovascular risk, and whether this risk was modifiable among patients receiving statins in the TNT trial. Methods -Patients with coronary heart disease [CHD] and LDL-C 130-250mg/dL entered an 8-week run-in phase with atorvastatin 10mg/day (ATV10)...
April 4, 2018: Circulation
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
#11
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...
May 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29588315/cholesterol-efflux-pathways-suppress-inflammasome-activation-netosis-and-atherogenesis
#12
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
#13
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
#14
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
#15
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
#16
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...
June 2018: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/29617722/pcsk9-regulates-expression-of-scavenger-receptors-and-ox-ldl-uptake-in-macrophages
#17
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
#18
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
#19
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
#20
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
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