Is the carotid intima-media thickness really a good surrogate marker of atherosclerosis?

AIM: Intima-media thickness (IMT) is considered a surrogate measurement of atherosclerosis but this is still under debate. METHODS: To evaluate the relationship between carotid IMT and atherosclerosis, postmortem specimens of the distal segments of the left common carotid artery (CCA) from 133 Korean men aged from 20 to 78 years were used for histopathology and computer-assisted morphometry. Blood lipids and atherosclerosis-associated collagen and elastin were quantitatively analyzed. RESULTS: Correlation coefficients of IMT were smaller than those of intima thickness but IMT was well associated with age (r= 0.55, p <0.00001), atherosclerosis score (or grade, AS, r= 0.73, p < 0.00001), plaque area (PA, r= 0.72, p <0.00001), total cholesterol (TC, r= 0.69, p <0.00001), low-density lipoprotein cholesterol (LDL-c, r= 0.72, p <0.00001) and triglyceride (TG, r= 0.38, p < 0.001). Coronary artery stenosis (CAS) and coronary calcification were also well associated with age (p <0.00001), IMT (p <0.005) and PA (p <0.00001). When IMT was thicker than 1 mm, the possibility of carotid atherosclerosis accompanied with CAS and coronary calcification, TC, LDL-c and TG was much higher (CAS with coronary calcification,p <0.005; TC, p <0.00001; LDL-c, p < 0.00005; TG, p <0.00001). Collagen tended to increase while elastin tended to decrease as AS increased (p <0.005); collagen increased and elastin decreased (p <0.00001) when comparing plaque to the plaque-free area in the same segment. CONCLUSION: These results support that the carotid IMT in association with TC, LDL-c and TG can be used as a good surrogate marker of atherosclerosis and predictor of coronary heart disease. Plaque formation may influence significant quantitative changes in collagen and elastin.

CD36 signaling inhibits the translation of heat shock protein 70 induced by oxidized low density lipoprotein through activation of peroxisome proliferators-activated receptor gamma.

Oxidized LDL (OxLDL), a causal factor in atherosclerosis, induces the expression of heat shock proteins (Hsp) in a variety of cells. In this study, we investigated the role of CD36, an OxLDL receptor, and peroxisome proliferator-activated receptor gamma (PPARgamma) in OxLDL-induced Hsp70 expression. Overexpression of dominant-negative forms of CD36 or knockdown of CD36 by siRNA transfection increased OxLDL-induced Hsp70 protein expression in human monocytic U937 cells, suggesting that CD36 signaling inhibits Hsp70 expression. Similar results were obtained by the inhibition of PPARgamma activity or knockdown of PPARgamma expression. In contrast, overexpression of CD36, which is induced by treatment of MCF-7 cells with troglitazone, decreased Hsp70 protein expression induced by OxLDL. Interestingly, activation of PPARgamma through a synthetic ligand, ciglitazone or troglitazone, decreased the expression levels of Hsp70 protein in OxLDL-treated U937 cells. However, major changes in Hsp70 mRNA levels were not observed. Cycloheximide studies demonstrate that troglitazone attenuates Hsp70 translation but not Hsp70 protein stability. PPARgamma siRNA transfection reversed the inhibitory effects of troglitazone on Hsp70 translation. These results suggest that CD36 signaling may inhibit stress- induced gene expression by suppressing translation via activation of PPARgamma in monocytes. These findings reveal a new molecular basis for the anti-inflammatory effects of PPARgamma.

Quantitative analysis of aortic atherosclerosis in Korean female: a necropsy study.

To assess the regional difference and influence of the biological variables on atherosclerosis in female, we analyzed 7 segments of aorta (2 ascending, 3 thoracic, and 2 abdominal) from 90 superficially healthy Korean women (39+/-14 yr of age) who died from external causes. Tissue specimens were macroscopically examined and histopathologically divided into 7 grades for scoring (ATHERO, from 0=intact, to 6=thrombi formation). Lumen diameter (LD), wall thickness (WT), intima thickness (INT), and media thickness (MED) were obtained by computed morphometry. Atherosclerosis was common in the distal infrarenal (C2), proximal thoracic (B1), and proximal ascending (A1) segments. Total 95.6% of all subjects had atherosclerosis of variable degree in one or more segments, but an aneurysmal change was not found. The number of atherosclerotic segments and atherosclerosis score in the 7 segments increased with aging. However, the body size did not affect the aortic size and ATHERO. With aging, LD and INT of the A1, B1 and C2 increased (p<.00001); WT of the B1 and C2 increased (p<.01); and MED of C2 decreased (p<.01). LD and WT of the B1 and C2 (p<.05), INT of the A1, B1 and C2 (p<.00001) increased, and MED of C2 decreased (p<.01) with ATHERO. These data suggest that age is simple but a reliable parameter for estimating the progression of atherosclerosis.

Motor branch of the rectus femoris: anatomic location for selective motor branch block in stiff-legged gait.

OBJECTIVE: To determine the ideal target point for selective motor branch block of the rectus femoris to treat stiff-legged gait. DESIGN: Descriptive study. SETTING: Anatomic institute of a university school of medicine in Korea. CADAVERS: Twenty-two preserved adult cadavers. INTERVENTION: The anterior thigh of the cadaver was dissected below the inguinal ligament. The motor branches of the 4 heads of the quadriceps were identified and traced from just below the inguinal ligament to the motor points. MAIN OUTCOME MEASURES: The point T, where the motor branch of the rectus femoris is divided into smaller subbranches, was identified. Its location in relation to the surface anatomic landmarks was determined on the basis of the 2 anatomic lines that connect the anterior superior iliac spine to the medial femoral condyle, and the issuing spot of the femoral nerve below the inguinal ligament to the middle of the superior pole of the patellar. RESULTS: The motor branch of the rectus femoris was divided into 2 subbranches at point T just before it reached the muscle. It nearly touched the medial margin of the rectus femoris at a proximal one-fourth to one-fifth point on 2 anatomic lines. The superior subbranch penetrated the muscle fascia at the posterior surface of the proximal one third of the muscle, whereas the inferior subbranch penetrated the muscle fascia at the medial border of the muscle. CONCLUSION: The point T is the most suitable target point to selectively block the motor branch of the rectus femoris without affecting the other 3 motor branches of the femoral nerve in the treatment of stiff-legged gait.

Infarct size-limiting effect of calcium preconditioning in rabbit hearts.

Recent studies demonstrated that brief period of Ca2+ depletion and repletion (Ca2+ preconditioning, CPC) has strong protective effects against ischemia in a rat heart. CPC and classic preconditioning (IPC) were compared in relation with infarct size and protein kinase C (PKC) isozymes. Isolated Langendorff-perfused rabbit hearts were subjected to 45-min ischemia (Isc) followed by 120-min reperfusion (R) with or without IPC, induced by 5-min Isc and 10-min R. In the CPC hearts, 5-min Ca2+ depletion and 10-min repletion (CPC) were given before 45-min Isc, with or without concurrent PKC inhibition (calphostin C, 200 nmol/L). IPC enhanced recovery of LV function, while CPC did not. Infarct size was significantly reduced by both CPC and IPC (p < 0.05 vs. ischemic control). Membrane PKC was significantly increased from 2.53 +/- 0.07 (baseline, nmol/g tissue) to 3.11+/-0.07, 3.34 +/- 0.11, 3.15 +/- 0.09, and 3.06 +/- 0.08 by IPC, IPC and 45-min Isc, CPC and 45-min Isc, respectively (p < 0.01). Immunoblots of membrane PKC were increased by IPC, IPC and 45-min Isc, and CPC. These effects were abolished by PKC inhibition. Thus, activation of PKC may have trigger role in the mechanism of cardioprotective effect by CPC.