Cholesterol in human atherosclerotic plaque is a marker for underlying disease state and plaque vulnerability

Abstract

BackgroundCholesterol deposition in arterial wall drives atherosclerosis. The key goal of this study was to examine the relationship between plaque cholesterol content and patient characteristics that typically associate with disease state and lesion vulnerability. Quantitative assays for free cholesterol, cholesteryl ester, triglyceride, and protein markers in atherosclerotic plaque were established and applied to plaque samples from multiple patients and arterial beds (Carotid and peripheral arteries; 98 lesions in total).ResultsWe observed a lower cholesterol level in restenotic than primary peripheral plaque. We observed a trend toward a higher level in symptomatic than asymptomatic carotid plaque. Peripheral plaque from a group of well-managed diabetic patients displayed a weak trend of more free cholesterol deposition than plaque from non-diabetic patients. Plaque triglyceride content exhibited less difference in the same comparisons. We also measured cholesterol in multiple segments within one carotid plaque sample, and found that cholesterol content positively correlated with markers of plaque vulnerability, and negatively correlated with stability markers.ConclusionsOur results offer important biological validation of cholesterol as a key lipid marker for plaque severity. Results also suggest cholesterol is a more sensitive plaque marker than routine histological staining for neutral lipids.

Higher Visit-to-Visit Low-Density Lipoprotein Cholesterol Variability Is Associated With Lower Cognitive Performance, Lower Cerebral Blood Flow, and Greater White Matter Hyperintensity Load in Older Subjects

“…18 Thus, varying levels of LDL-C could theoretically lead to fluctuations in the composition of atherosclerotic plaques, possibly inducing plaque instability and thereby increasing the risk of (sub)clinical cerebrovascular damage. 19 Another pathway might be through endothelial dysfunction, which…”

“…18 Por lo tanto, los niveles variables de LDL-C en teoría podrían llevar a fluctuaciones en la composición de las placas ateroescleróticas, que pueden inducir inestabilidad de la placa y de este modo aumentar el riesgo de daño cerebrovascular (sub)clínico. 19 Otra vía podría ser a través de la disfunción endotelial, la cual puede ser causada por muchos de los factores de riesgo que predisponen a la ateroesclerosis. 20 Debido a que los individuos con marcadores séricos elevados de disfunción endotelial tienen mayor riesgo de desarrollar deterioro cognitivo, 21 posiblemente a través de cambios en el flujo sanguíneo cerebral, 22,23 una mayor variabilidad del LDL-C podría causar deterioro cognitivo.…”

High-Throughput Simultaneous Analysis of RNA, Protein, and Lipid Biomarkers in Heterogeneous Tissue Samples

“…2, Applied Biosystems). The TLDA genes were: phospholipase A2, group VII (platelet-activating factor acetylhydrolase, plasma) (PLA2G7) 4 ; dual specificity phosphatase 1 (DUSP1); chemokine (C-C motif) ligand 2 (CCL2); arachidonate 5-lipoxygenase-activating protein (ALOX5AP); adenosylhomocysteinase (AHCY); prostaglandinendoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) (PTGS2); heme oxygenase (decycling) 1 (HMOX1); myeloperoxidase (MPO); chemokine (C-C motif) receptor 1 (CCR1); chemokine (C-C motif) ligand 7(CCL7); endogeneous control eukaryotic 18S ribosomal RNA (4342379-18S); vascular cell adhesion molecule 1 (VCAM1); CD5 molecule-like (CD5L); FBJ murine osteosarcoma viral oncogene homolog (FOS); ATP-binding cassette, sub-family A (ABC1), member 1 (ABCA1); tumor necrosis factor (TNF); hydroxycarboxylic acid receptor 3 (HCAR3); platelet-activating factor receptor (PTAFR); chemokine (C-C motif) ligand 3 (CCL3); matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) (MMP9); matrix metallopeptidase 1 (interstitial collagenase) (MMP1); glyceraldehyde-3-phosphate dehydrogenase (GAPDH); chemokine (C-X-C motif) ligand 2 (CXCL2); interleukin 8 (IL8); arachidonate 5-lipoxygenase (ALOX5); cystathioninebeta-synthase (CBS); cysteinyl leukotriene receptor 2 (CYSLTR2); CD163 molecule (CD163); early growth response 2 (EGR2); chemokine (C-C motif) ligand 5…”

“…Pellets from protein extraction were extracted with chloroform:methanol (2:1) according to the method of Folch et al (3 ) as modified by Chen et al (4 ). Sample size was determined by size of the sample used for protein extraction.…”

Original article Circulated CD4 + CD28 - lymphocytes rate and their cytotoxicity and morphological parameters of internal carotid artery atheromatous plaques in patients with atherosclerosis-related ischemic stroke

“…Cholesterol crystals within atherosclerotic lesions are recognized as a potent factor promoting inflammation in the wall of an arterial vessel, which results in a cascade of events leading to plaque destabilization [1,4,25]. Other researchers suggest that CD4 + CD28 -Lc appear originally in the blood and then infiltrate tissues, including atheromatous lesions, in which they enhance inflammatory mechanisms [27].…”