Associations of circulating biomarkers with the presence and severity of coronary, carotid and femoral arterial atherosclerosis

Aim. To identify and characterize the associations of the presence and severity of atherosclerosis of various localization with the blood level of biochemical parameters, as well as to assess the potential of their use as markers of metabolic disorders with increased atherogenic potential.Material and methods. The study included 216 patients (men, 53%) aged 24-87 years (mean age, 61,5±10,73 years). All patients underwent coronary angiography, carotid (CA) and femoral arterial (FA) duplex ultrasound to assess the presence and severity of atherosclerosis. In blood serum/plasma, biochemical parameters were analyzed using standard methods.Results. Based on the analysis of circulating biomarker profile, diagnostic complexes have been established that allow assessing atherosclerosis of different localization. According to the data obtained, the determinants of coronary and CA atherosclerosis are endothelial dysfunction (concentration of nitric oxide metabolites <36,0 μmol/L) and an increased level of creatinine (≥73,0 μmol/L). The specific markers associated with severe atherosclerosis of coronary and FAs (but not CA) were low high-density lipoprotein cholesterol (≤1,0/1,2 μmol/L for male/ female, respectively) and an increased C-reactive protein level (≥1,0 mg/l). Severe peripheral atherosclerosis (CA and FA involvement) was associated with hyperglycemia (glucose ≥6,1 μmol/L), while severe FA atherosclerosis — with hyperinsulinemia (insulin ≥14,0 μU/ml).Conclusion. The analysis of associations of circulating biochemical parameters with atherosclerosis localization and severity revealed a number of metabolic markers associated with the increased atherogenic potential. It is possible to distinguish both universal parameters that are associated with atherosclerosis, regardless of its localization and/or severity, and specific biomarkers that characterize either the localization or the severity of atherosclerosis, or both.

Myxedema Coma and Acute Hepatopathy in a Dog with Severe Atherosclerosis

A 9-year-old male intact mixed-breed dog was presented to The Ohio State University Veterinary Medical Center for evaluation of two days’ duration of weakness, lethargy, inappetence, and one episode of vomiting the day of presentation. On presentation, the dog was depressed and tetraparetic. He was noted to be icteric and dehydrated. Obesity and truncal alopecia with a “rat tail” appearance were observed. Diagnostic testing revealed evidence of an acute hepatopathy and peritonitis. Given the dog’s neurologic status, physical examination abnormalities, including a “tragic facial expression”, and hyperlipidemia, there was concern for possible myxedema coma. A thyroid panel was consistent with hypothyroidism. The dog experienced respiratory arrest prior to initiation of therapy, and an autopsy confirmed the presence of subacute necrotizing cholangiohepatitis, marked atherosclerosis, and severe thyroid atrophy. These clinical and pathologic changes were supportive of myxedema coma.

Medicolegal evaluation of pontine hemorrhage at autopsy- Highlights from a case and an overview

One in ten non-traumatic intracerebral hemorrhages (ICH) is located in the pons with chronic arterial hypertension as the leading etiology. In the forensic context, deaths related to a pontine hemorrhage (PH) are usually encountered in situations of drug abuse, excited delirium, trauma, as well as in sudden natural deaths where some hypertensive catastrophe is the usual underlying mechanism. The clinical presentation of PH may be variable, causing a failure in timely diagnosis that, if presents with unexplainable circumstances, may become the subject of medicolegal concern. The present case relates to a middle-aged man with a long history of hypertension and presents during an afternoon with an abrupt onset of deleterious symptoms. The patient was managed conservatively but succumbed to his illness and expires during treatment. A questionable diagnosis and the case circumstances, however, directed the doctors to inform the police. A medicolegal autopsy was therefore carried out that leads to the discovery of a lethal pontine hemorrhage rupturing into the fourth ventricle and involving the adjacent cerebellar tissues as well. Severe atherosclerosis of the basal arteries constituting Circle of Willis and Vertebrobasilar system was seen along with their hallmark effects that became evident during brain sectioning. Pathological stigmata of well established hypertension were found in the heart and kidneys. A clinic pathological correlation of the physical characteristics and topography of the hematoma to its severity was also carried out, based upon the known CT and autopsy findings. The possibility of a drug related or traumatic and secondary brainstem/Duret hemorrhage was ruled out.

CREBH Systemically Regulates Lipid Metabolism by Modulating and Integrating Cellular Functions

Cyclic AMP-responsive element-binding protein H (CREBH, encoded by CREB3L3) is a membrane-bound transcriptional factor expressed in the liver and small intestine. The activity of CREBH is regulated not only at the transcriptional level but also at the posttranslational level. CREBH governs triglyceride metabolism in the liver by controlling gene expression, with effects including the oxidation of fatty acids, lipophagy, and the expression of apolipoproteins related to the lipoprotein lipase activation and suppression of lipogenesis. The activation and functions of CREBH are controlled in response to the circadian rhythm. On the other hand, intestinal CREBH downregulates the absorption of lipids from the diet. CREBH deficiency in mice leads to severe hypertriglyceridemia and fatty liver in the fasted state and while feeding a high-fat diet. Therefore, when crossing CREBH knockout (KO) mice with an atherosclerosis model, low-density lipoprotein receptor KO mice, these mice exhibit severe atherosclerosis. This phenotype is seen in both liver- and small intestine-specific CREBH KO mice, suggesting that CREBH controls lipid homeostasis in an enterohepatic interaction. This review highlights that CREBH has a crucial role in systemic lipid homeostasis to integrate cellular functions related to lipid metabolism.

Clinical case of a patient with occlusive thrombosis of the right common carotid artery

The paper presents a case of a patient with floating thrombosis in the right common carotid artery and occlusion of the carotid bifurcation of the right common carotid artery against the background of severe atherosclerosis of the common carotid artery with 70% stenosis. Thrombosis was identified using color duplex ultrasound scanning in an asymptomatic patient. During hospitalization, thrombosis was complicated by a cerebral infarction of the right middle cerebral artery, apparently of embolic origin.

Lenin’s Stroke

Lenin’s stroke remains a matter of debate. Here, we propose to assess the potential mechanisms. Lenin died on January 21, 1924 at the age of 53 years. Although some doctors suggested that the origin of his health problems was neurosyphilis, the autopsy findings were consistent with a severe atherosclerosis. This process might account for his recurrent ischemic strokes. In view of the family vascular history, an early hereditary atherosclerosis may be proposed.

Atherothrombosis model by silencing of protein C in APOE*3-Leiden.CETP transgenic mice

Murine atherosclerosis models are key for investigation of atherosclerosis pathophysiology and drug development. However, they do not feature spontaneous atherothrombosis as a final stage of atherosclerosis. Transgenic mice expressing both the human mutant apolipoprotein E form APOE*3-Leiden and human cholesteryl ester transfer protein (CETP), i.e. APOE*3-Leiden.CETP mice, feature a moderate hyperlipoproteinemia and atherosclerosis phenotype. In contrast to apolipoprotein E deficient (Apoeˉ/ˉ) mice, APOE*3-Leiden.CETP mice respond well to lipid-lowering and anti-atherosclerotic drugs. The aim of the study was to investigate whether silencing of anticoagulant Protein C (Proc) allows APOE*3-Leiden.CETP mice to feature thrombosis as a final stage of atherosclerosis. Female APOE*3-Leiden.CETP mice were fed a Western-type diet to induce advanced atherosclerosis, followed by an injection with a small interfering RNA targeting Proc (siProc). Presence of atherosclerosis and atherothrombosis was determined by histologic analysis of the aortic root. Atherosclerosis severity in the aortic root area of APOE*3-Leiden.CETP mice varied from type “0” (no lesions) to type “V” lesions (advanced and complex lesions). Atherothrombosis following siProc injection was observed for 4 out of 21 APOE*3-Leiden.CETP mice (19% incidence). The atherothrombosis presented as large, organized, fibrin- and leukocyte-rich thrombi on top of advanced (type “V”) atherosclerotic plaques in the aortic root. This atherothrombosis was comparable in appearance and incidence as previously reported for Apoeˉ/ˉ mice with a more severe atherosclerosis (19% incidence). APOE*3-Leiden.CETP mice with modest hyperlipidemia and atherosclerosis can develop atherothrombosis upon transient Proc-silencing. This further extends the use of these mice as a test model for lipid-lowering and anti-atherosclerotic drugs.

Antibodies against apoB100 peptide 210 inhibit atherosclerosis in apoE-/- mice

Atherosclerotic plaques are characterized by an accumulation and subsequent oxidation of LDL, resulting in adaptive immune responses against formed or exposed neoepitopes of the LDL particle. Autoantibodies against native p210, the 3136–3155 amino acid sequence of the LDL protein apolipoprotein B-100 (apoB100) are common in humans and have been associated with less severe atherosclerosis and decreased risk for cardiovascular events in clinical studies. However, whether apoB100 native p210 autoantibodies play a functional role in atherosclerosis is not known. In the present study we immunized apoE-/- mice with p210-PADRE peptide to induce an antibody response against native p210. We also injected mice with murine monoclonal IgG against native p210. Control groups were immunized with PADRE peptide alone or with control murine monoclonal IgG. Immunization with p210-PADRE induced an IgG1 antibody response against p210 that was associated with reduced atherosclerotic plaque formation in the aorta and reduced MDA-LDL content in the lesions. Treatment with monoclonal p210 IgG produced a similar reduction in atherosclerosis as immunization with p210-PADRE. Our findings support an atheroprotective role of antibodies against the apoB100 native p210 and suggest that vaccines that induce the expression of native p210 IgG represent a potential therapeutic strategy for lowering cardiovascular risk.