Risk factors for atherosclerosis and the development of preatherosclerotic intimal hyperplasia

Abstract

Summary-Intimal hyperplasia or thickening is considered to be the precursor lesion for atherosclerosis in humans; however the factors governing its formation are unclear. In the atherosclerosis-resistant internal thoracic artery, pre-atherosclerotic intimal hyperplasia routinely forms during adulthood after the 4th decade and is associated with at least two traditional risk factors for atherosclerosis: age and smoking.Background-Intimal hyperplasia, or thickening, is considered to be the precursor lesion for atherosclerosis in humans; however, the factors governing its formation are unclear. To gain insight into the etiology of pre-atherosclerotic intimal hyperplasia, traditional risk factors for atherosclerosis were correlated with the intimal hyperplasia in an atherosclerosis-resistant vessel, the internal thoracic artery.Methods-Paired internal thoracic arteries were obtained from 89 autopsies. Multivariate logistic regression and multiple regression models were used to examine the association of preatherosclerotic intimal hyperplasia with traditional risk factors for atherosclerosis: age, gender, hypertension, smoking, body mass index, diabetes, and hypercholesterolemia.Results-Atherosclerotic lesions consisting of fatty streaks and/or type III intermediate lesions were identified in 19 autopsies. Only age >75 years was found to be significantly correlated with atherosclerotic lesion development (P=0.01). Multiple regression model of the intima/media ratio in all 89 cases revealed age >75 years (P<0.0001), age 51-75years (P=0.0012), smoking (P=0.008) and hypertension (P=0.02) to be significantly correlated with intimal thickness. In the 70 cases without atherosclerosis, only age 51-75 years (P=0.006) and smoking (P=0.028) were found to be significantly associated with pre-atherosclerotic intimal thickening.Conclusions-In the atherosclerosis-resistant internal thoracic artery, pre-atherosclerotic intimal hyperplasia routinely forms during adulthood after the 4th decade and is associated with at least two traditional risk factors for atherosclerosis: age and smoking. These observations indicate that in some settings, intimal hyperplasia may be part of the disease process of atherosclerosis, and that its formation may be influenced by traditional risk factors for atherosclerosis.

Modelling atherosclerosis by proteomics: Molecular changes in the ascending aortas of cholesterol-fed rabbits

“…The prominent thickening in the intimal region of the arterial wall observed in all five HCDtreated subjects is consistent with intimal thickening/hyperplasia, the precursor lesion of atherosclerosis [15]. This strongly suggests that the HCD treated animals employed in this study were progressing towards overt atherosclerosis in response to the dramatically elevated blood cholesterol levels seen for this group.…”

“…A C C E P T E D ACCEPTED MANUSCRIPT 6 The labelled digest was fractionated on a 0.3 x 35 mm Zorbax Bio-SCX II column (Agilent, Santa Clara, CA, USA) in an on-line fashion using 10 µL aliquots of KCl in 0.1% (v/v) formic acid (15,25,40,60,80,100,120,150,200, and 600 mM). Peptides were captured on a 0.3…”

Endogenous endothelin-1 and femoral artery shear rate

“…Furthermore, based on the current findings, it appears that reduced antegrade shear rate, and not augmented retrograde shear rate, recognized in the arms of the elderly, likely plays an essential role in the age-related reduction in mean shear rate and subsequent development of atherosclerosis in the legs. In support of this contention, antegrade shear rate was significantly and negatively correlated with IMT and IMT normalized for CFA, revealing an association between antegrade shear rate and a recognized atherosclerotic risk factor [43] in these healthy individuals.…”

Pathology of myocardial infarction, coronary artery disease, plaque disruption, and the vulnerable atherosclerotic plaque

“…There is an initial phase of vascular wall activation, characterized by the formation of intimal hyperplasia or intimal thickening. 5,8,9 This intimal hyperplasia is largely composed of intimal smooth muscle cells and proteoglycans, and typically initially forms in an eccentric fashion, indicating an etiological role for variable shear stress ( Figure 2). This early phase of intimal thickening is not well recapitulated in mouse models of human atherosclerosis, and thus is not included in most reviews on atherosclerosis written primarily from a mouse pathology perspective.…”

“…3,4 This persistent elevated risk in former smokers may be due to promotion of a premature atherosclerotic burden in those who smoke. 5 In addition to more traditional risk factors, the elevation of serum inflammatory markers, such as C-reactive protein and myeloperoxidase (MPO), are becoming increasingly recognized as important aids in assessing risk of atherosclerotic coronary artery disease.…”