OBJECTIVE: Atherosclerosis is a chronic lipid-driven inflammatory disease of the arterial wall. Due to its cardiovascular ischemic complications, it is one of the most common causes of death in people. However, atherosclerosis is seldomly reported in dogs.
METHODS: A 10-year-old male mixed-breed dog.
UNASSIGNED: Severe acute kidney injury associated with thrombosis of the abdominal aorta.
RESULTS: Treatment included renal replacement therapy, antithrombotic therapy, and supportive care. However, the dog developed neurological and respiratory complications and was euthanized due to worsening kidney function and lack of improvement of the thrombosis. Postmortem examination confirmed the presence of aortic thromboembolism and renal infarcts. Histology revealed severe chronic-active atherosclerosis of the distal aorta and renal arteries.
CONCLUSIONS: Aortic thrombosis is uncommon in dogs, and it is often associated with underlying conditions such as protein-losing nephropathy, endocrine disorders, cardiac disease, or hypercoagulability. In this case, no specific underlying cause was identified and atherosclerosis was considered the primary cause of the thrombosis.

Atherosclerosis and resulting cardiovascular disease are the leading causes of death in the US. Hyperhomocysteinemia (HHcy), or the accumulation of the intermediate amino acid homocysteine, is an independent risk factor for atherosclerosis, but the intricate biological processes mediating this effect remain elusive. Several factors regulate homocysteine levels, including the activity of several enzymes and adequate levels of their coenzymes, including pyridoxal phosphate (vitamin B6), folate (vitamin B9), and methylcobalamin (vitamin B12). To better understand the biological influence of HHcy on the development and progression of atherosclerosis, apolipoprotein-E-deficient (apoE-/- mice), a model for human atherosclerosis, were fed a hyperhomocysteinemic diet (low in methyl donors and B vitamins) (HHD) or a control diet (CD). After eight weeks, the plasma, aorta, and liver were collected to quantify methylation metabolites, while plasma was also used for a broad targeted metabolomic analysis. Aortic plaque burden in the brachiocephalic artery (BCA) was quantified via 14T magnetic resonance imaging (MRI). A severe accumulation of plasma and hepatic homocysteine and an increased BCA plaque burden were observed, thus confirming the atherogenic effect of the HHD. Moreover, a decreased methylation capacity in the plasma and aorta, indirectly assessed by the ratio of S-adenosylmethionine to S-adenosylhomocysteine (SAM:SAH) was detected in HHD mice together with a 172-fold increase in aortic cystathionine levels, indicating increased flux through the transsulfuration pathway. Betaine and its metabolic precursor, choline, were significantly decreased in the livers of HHD mice versus CD mice. Widespread changes in the plasma metabolome of HHD mice versus CD animals were detected, including alterations in acylcarnitines, amino acids, bile acids, ceramides, sphingomyelins, triacylglycerol levels, and several indicators of dysfunctional lipid metabolism. This study confirms the relevance of severe HHcy in the progression of vascular plaque and suggests novel metabolic pathways implicated in the pathophysiology of atherosclerosis.

Finasteride is commonly prescribed to treat benign prostate hyperplasia and male-pattern baldness in cis men and, more recently, trans individuals. However, the effect of finasteride on cardiovascular disease remains elusive. We evaluated the role of finasteride on atherosclerosis using low-density lipoprotein (LDL) receptor-deficient (Ldlr-/-) mice. Next, we examined the relevance to humans by analyzing the data deposited between 2009 and 2016 in the National Health and Nutrition Examination Survey. We show that finasteride reduces total plasma cholesterol and delays the development of atherosclerosis in Ldlr-/- mice. Finasteride reduced monocytosis, monocyte recruitment to the lesion, macrophage lesion content, and necrotic core area, the latter of which is an indicator of plaque vulnerability in humans. RNA sequencing analysis revealed a downregulation of inflammatory pathways and an upregulation of bile acid metabolism, oxidative phosphorylation, and cholesterol pathways in the liver of mice taking finasteride. Men reporting the use of finasteride showed lower plasma levels of cholesterol and LDL-cholesterol than those not taking the drug. Our data unveil finasteride as a potential treatment to delay cardiovascular disease in people by improving the plasma lipid profile.

BACKGROUND: Carotid free-floating thrombus (CFFT) is an uncommon disorder. The aim of this study was to describe a French cohort of CFFT patients.
METHODS: We conducted a retrospective monocentric study from a Stroke Center among patients admitted for stroke with CFFT.
RESULTS: Between January 2017 to December 2019, 2038 ischemic strokes were recorded. A total of 50 patients with CFFT were consecutively included (32 men/18 women). The mean age was 58.2 years (±11.7). Their etiologies were atheroma (46%), carotid dissection and web (20%), hypercoagulability disorders (16%) and arrhythmia (10%). Exclusive medical management was performed in 38 patients (76%): 29 (59.2%) were anticoagulated and 9 (18.4%) received antiplatelets alone in the first week. Surgical intervention was performed in the first 30 days for 11 patients (22%). The main surgical indication was a residual carotid stenosis over 70%. Only three patients had a recurrent stroke in the medical group with anticoagulants. No patients in the antiplatelet group or the surgical group had a recurrent stroke.
CONCLUSIONS: Our study summarized a large cohort of 50 patients with CFFT. This diagnosis implies the need to search for a local arterial disease and to screen for hypercoagulability states. An initial medical strategy followed by a delayed carotid surgery if the follow-up imaging shows a residual stenosis appears to be safe.

OBJECTIVE: Dyslipidemia causes metabolic disorders such as atherosclerosis and fatty liver syndrome due to abnormally high blood lipids. Purple perilla frutescens extract (PPE) possesses various bioactive compounds such as α-asarone, chlorogenic acid and rosmarinic acid. This study examined whether PPE and α-asarone improved dyslipidemia-associated inflammation and inhibited atheroma formation in apolipoprotein E (apoE)-deficient mice, an experimental animal model of atherosclerosis.
METHODS: ApoE-deficient mice were fed on high cholesterol-diet (Paigen\'s diet) and orally administrated with 10-20 mg/kg PPE and α-asarone for 10 wk.
RESULTS: The Paigen\'s diet reduced body weight gain in apoE-deficient mice, which was not restored by PPE or α-asarone. PPE or α-asarone improved the plasma lipid profiles in Paigen\'s diet-fed apoE-deficient mice, and despite a small increase in high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol, and very LDL were significantly reduced. Paigen\'s diet-induced systemic inflammation was reduced in PPE or α-asarone-treated apoE-deficient mice. Supplying PPE or α-asarone to mice lacking apoE suppressed aorta atherogenesis induced by atherogenic diet. PPE or α-asarone diminished aorta accumulation of CD68- and/or F4/80-positive macrophages induced by atherogenic diet in apoE-deficient mice. Treatment of apoE-deficient mice with PPE and α-asarone resulted in a significant decrease in plasma cholesteryl ester transfer protein level and an increase in lecithin:cholesterol acyltransferase reduced by supply of Paigen\'s diet. Supplementation of PPE and α-asarone enhanced the transcription of hepatic apoA1 and SR-B1 reduced by Paigen\'s diet in apoE-deficient mice.
CONCLUSIONS: α-Asarone in PPE inhibited inflammation-associated atheroma formation and promoted hepatic HDL-C trafficking in dyslipidemic mice.

Lipid-laden foam cells within atherosclerotic plaques are key players in all phases of lesion development including its progression, necrotic core formation, fibrous cap thinning, and eventually plaque rupture. Manipulating foam cell biology is thus an attractive therapeutic strategy at early, middle, and even late stages of atherosclerosis. Traditional therapies have focused on prevention, especially lowering plasma lipid levels. Despite these interventions, atherosclerosis remains a major cause of cardiovascular disease, responsible for the largest numbers of death worldwide.
Foam cells within atherosclerotic plaques are comprised of macrophages, vascular smooth muscle cells, and other cell types which are exposed to high concentrations of lipoproteins accumulating within the subendothelial intimal layer. Macrophage-derived foam cells are particularly well studied and have provided important insights into lipid metabolism and atherogenesis. The contributions of foam cell-based processes are discussed with an emphasis on areas of therapeutic potential and directions for drug development.
As key players in atherosclerosis, foam cells are attractive targets for developing more specific, targeted therapies aimed at resolving atherosclerotic plaques. Recent advances in our understanding of lipid handling within these cells provide insights into how they might be manipulated and clinically translated to better treat atherosclerosis.

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UNASSIGNED: Fatty streaks initiating the formation of atheromatous plaque appear in the tunica intima. The tunica media is not known to be a nidus for lipid accumulation initiating atherogenesis. We assessed changes to the tunica media in response to a micro-injury produced in the pig aorta. In addition, we assessed human carotid endarterectomy plaques for indication of atheroma initiation in the tunica media.
UNASSIGNED: Three healthy landrace female pigs underwent laparotomy to inject autologous blood and create micro-hematomas at 6 sites within the tunica media of the infrarenal abdominal aorta. These pigs were fed a high-fat diet (HFD) for 4-12 weeks. Post-mortem aortas from all pigs, including a control group of healthy pigs, were serially stained to detect lipid deposits, vasa vasora (VV), immune cell infiltration and inflammatory markers, as well as changes to the vascular smooth muscle cell (vSMC) compartment. Moreover, 25 human carotid endarterectomy (CEA) specimens were evaluated for their lipid composition in the tunica media and intima.
UNASSIGNED: High lipid clusters, VV density, and immune cell infiltrates were consistently observed at 5 out of 6 injection sites under prolonged hyperlipidemia. The hyperlipidemic diet also affected the vSMC compartment in the tunica media adjacent to the tunica adventitia, which correlated with VV invasion and immune cell infiltration. Analysis of human carotid specimens post-CEA indicated that 32% of patients had significantly greater atheroma in the tunica media than in the arterial intima.
UNASSIGNED: The arterial intima is not the only site for atherosclerosis initiation. We show that injury to the media can trigger atherogenesis.

The article describes how atherosclerosis and coronavirus disease 19 (COVID-19) may affect each other. The features of this comorbid pathogenesis at various levels (vascular, cellular and molecular) are considered. A bidirectional influence of these conditions is described: the presence of cardiovascular diseases affects different individuals\' susceptibility to viral infection. In turn, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can have a negative effect on the endothelium and cardiomyocytes, causing blood clotting, secretion of pro-inflammatory cytokines, and thus exacerbating the development of atherosclerosis. In addition to the established entry into cells via angiotensin-converting enzyme 2 (ACE2), other mechanisms of SARS-CoV-2 entry are currently under investigation, for example, through CD147. Pathogenesis of comorbidity can be determined by the influence of the virus on various links which are meaningful for atherogenesis: generation of oxidized forms of low-density lipoproteins (LDL), launch of a cytokine storm, damage to the endothelial glycocalyx, and mitochondrial injury. The transformation of a stable plaque into an unstable one plays an important role in the pathogenesis of atherosclerosis complications and can be triggered by COVID-19. The impact of SARS-CoV-2 on large vessels such as the aorta is more complex than previously thought considering its impact on vasa vasorum. Current information on the mutual influence of the medicines used in the treatment of atherosclerosis and acute COVID-19 is briefly summarized.

OBJECTIVE: Atheromas can be detected incidentally in routine dental cone beam computed tomography (CBCT) images. This study aims to assess prevalence and risk factors associated with these vascular lesions.
METHODS: The maxillofacial CBCTs of 458 subjects were evaluated and divided into 4 groups based on the presence of calcified atheroma: subjects with no calcified atheroma, subjects with intracranial calcified atheroma (ICA), subjects with extracranial calcified atheroma (ECA), and subjects exhibiting combined lesions. Age, sex, medical conditions, family history, and size were documented. Analysis of variance followed by a multiple comparison test was used for data satisfying parametric test assumptions. Chi-squared tests were used to assess categorical data. The Spearman Rho test was used to assess the correlation between the incidence of calcified atheroma and subjects\' medical condition.
RESULTS: Of the 458 CBCTs evaluated, 29.90% presented with calcified atheroma. Calcified atheroma prevalence was significantly higher in older patients versus younger patients (p = 0.004) and in males compared to females (p = 0.004). Males were more likely to have the combination of ICA and ECA, whereas females were more likely to have ICA alone (p ≤ 0.040). Patients with calcified atheroma were significantly more likely to have a history of hyperlipidemia (p = 0.001), hypertension (p = 0.001), and myocardial infarction/coronary artery diseases (p = 0.001). Overall, patients exhibiting both intracranial and extracranial lesions were more likely to have cardiovascular risk factors (p = 0.001).
CONCLUSIONS: Incidentally detected calcified atheromas in CBCTs are common. Subjects with combined atheroma lesions are at higher risk for cardiovascular disease. The diagnosis of incidental calcified atheromas in CBCT\'s warrants early referral to medical specialists, especially if there is no medical history of existing cardiovascular disease.