The ApoC-I Content of VLDL Particles is Associated with Plaque Size in Persons with Carotid Atherosclerosis

Previous studies have shown that postprandial triglyceride-rich lipoproteins (TRLs) are enriched with apolipoprotein-C-I (apoC-I) in healthy individuals with increased intima-media thickness and in patients with coronary artery disease. The purpose of the present study was to determine apoC-I in TRL in persons with carotid atherosclerosis and its relation to plaque area. A population-based case (n = 42)-control (n = 39) study was conducted in persons with carotid atherosclerosis, assessed by B-mode ultrasound, and healthy controls. VLDL (Sf 20-400) was isolated in the fasting state and 4 h after ingestion of a standard fat meal. In the fasting state, persons with carotid atherosclerosis had increased number of apoC-I per VLDL-particle compared to persons without carotid atherosclerosis (8.6 +/- 5.4 vs. 6.3 +/- 4.2, P = 0.018). Total plaque area increased linearly (P = 0.017) across tertiles of apoC-I per VLDL-particle. In the postprandial state, a similar increase in the number of apoC-I per VLDL-particle occurred in both cases and controls (P < 0.001), but no significant difference was observed between groups. The number of apoC-I per VLDL-particle in the fasting state was accompanied by delayed clearance of TRL in the postprandial state, and associated with cholesterol enrichment of the VLDL-particles. Our findings support the concept that the number of apoC-I per VLDL-particle may be of importance for initiation and progression of atherosclerosis.     

Brachial Artery Intima-Media Thickness and Echogenicity in Relation to Lipids and Markers of Oxidative Stress in Elderly Subjects:-The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) Study

The aim of the present study was to relate brachial artery intima-media thickness (IMT) and the grey scale median of the intima-media complex (IM-GSM) to traditional cardiovascular risk factors and markers of inflammation and oxidative stress. In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, a population-based study of 1016 subjects aged 70, brachial artery IMT and IM-GSM, who were evaluated by ultrasound. Lipids, thirteen markers of inflammation and nine markers of oxidative stress were measured. The Framingham risk score was related to IMT (p < 0.0001), but not to the IM-GSM. In univariate analysis, HDL-cholesterol, serum triglycerides, fasting glucose, smoking, HOMA insulin resistance index and oxidized LDL levels were related to IMT. HDL and LDL-cholesterol, triglycerides, VCAM-1, e-selectin, leukocyte count, conjugated diens, baseline conjugated diens (BCD)-LDL, antibodies to oxLDL, the GSSG/GSH glutathione ratio and homocysteine were related to IM-GSM. In multiple regression models, HDL-cholesterol, fasting glucose and oxLDL levels were the independently related to IMT (p = 0.01–0.04), while serum triglycerides, BCD-LDL and the GSSG/GSH ratio were independently related to IM-GSM (p = 0.0001–0.004). In conclusion, in addition to traditional lipid variables, markers of oxidative stress were associated with both thickness and echogenicity of the brachial artery intima-media complex. Thus, both thickness and echogenicity of the brachial artery intima-media complex might be useful biomarkers in the future.     

Protease-Activated Receptor 1 in Human Carotid Atheroma Is Significantly Related to Iron Metabolism,Plaque Vulnerability,and the Patient’s Age

(1) Background: Protease-activated receptor 1 (PAR1) has regulatory functions in inflammation, atherogenesis, and atherothrombosis. Chronic iron administration accelerates arterial thrombosis. Intraplaque hemorrhage and hemoglobin catabolism by macrophages are associated with dysregulated iron metabolism and atherosclerotic lesion instability. However, it remains unknown whether expressions of PAR1 in human atherosclerotic lesions are related to plaque severity, accumulation of macrophages, and iron-related proteins. We investigated the expression of PAR1 and its relation to the expression of ferritin and transferrin receptors in human carotid atherosclerotic plaques and then explored potential connections between their expressions, plaque development, and classical risk factors. (2) Methods: Carotid samples from 39 patients (25 males and 14 females) were immunostained with PAR1, macrophages, ferritin, and transferrin receptor. Double immunocytochemistry of PAR1 and ferritin was performed on THP-1 macrophages exposed to iron. (3) Results: PAR1 expression significantly increases with the patient’s age and the progression of human atherosclerotic plaques. Expressions of PAR1 are significantly correlated with the accumulation of CD68-positive macrophages, ferritin, and transferrin receptor 1 (TfR1), and inversely correlated with levels of high-density lipoprotein. In vitro, PAR1 is significantly increased in macrophages exposed to iron, and the expression of PAR1 is colocalized with ferritin expression. (4) Conclusions: PAR1 is significantly related to the progression of human atherosclerotic lesions and the patient’s age. PAR1 is also associated with macrophage infiltration and accumulation of iron metabolic proteins in human atherosclerotic lesions. Cellular iron-mediated induction of PAR1 and its colocalization with ferritin in macrophages may further indicate an important role of cellular iron in atherothrombosis.     

COPD,Pulmonary Fibrosis and ILAs in Aging Smokers: The Paradox of Striking Different Responses to the Major Risk Factors

Aging and smoking are associated with the progressive development of three main pulmonary diseases: chronic obstructive pulmonary disease (COPD), interstitial lung abnormalities (ILAs), and idiopathic pulmonary fibrosis (IPF). All three manifest mainly after the age of 60 years, but with different natural histories and prevalence: COPD prevalence increases with age to >40%, ILA prevalence is 8%, and IPF, a rare disease, is 0.0005–0.002%. While COPD and ILAs may be associated with gradual progression and mortality, the natural history of IPF remains obscure, with a worse prognosis and life expectancy of 2–5 years from diagnosis. Acute exacerbations are significant events in both COPD and IPF, with a much worse prognosis in IPF. This perspective discusses the paradox of the striking pathological and pathophysiologic responses on the background of the same main risk factors, aging and smoking, suggesting two distinct pathophysiologic processes for COPD and ILAs on one side and IPF on the other side. Pathologically, COPD is characterized by small airways fibrosis and remodeling, with the destruction of the lung parenchyma. By contrast, IPF almost exclusively affects the lung parenchyma and interstitium. ILAs are a heterogenous group of diseases, a minority of which present with the alveolar and interstitial abnormalities of interstitial lung disease.