Hypercholesterolemia and tissue-specific differential mRNA expression of type-1 5'-iodothyronine deiodinase under different selenium status in rats

Type-1 5'-iodothyronine deiodinase (5'-DI) is responsible for conversion of T4 to T3. Selenium (Se) is an integral part of this enzyme. Keeping in view the strong association between atherosclerosis and hypothyroidism, the present study examined the behavior of 5'-DI in liver, aorta and thyroid during hypercholesterolemia following different Se status, i.e., Se deficiency (0.02ppm), adequate (0.2ppm) and excess dose (1ppm) in SD male rats. Animals were fed a control or high-cholesterol diet (2%) for 1 and 2 months. 5'-DI activity and mRNA expression was measured by RIA and RT-PCR respectively. In liver and aorta, 5'-DI expression significantly decreased with the Se-deficient and the high-cholesterol diet. The trend was opposite in thyroid, i.e., mRNA expression increased significantly during selenium deficiency and with a high-cholesterol feeding. But with 1ppm Se supplementation, the 5'-DI expression increased in all the three tissues. The present study indicates that hypercholesterolemia along with selenium deficiency is co-responsible for differential regulation of 5'-DI enzyme in thyroidal vs. extrathyroidal tissues. Distinct regulation of 5'-DI in the thyroid reflects the clinical importance of this selenoprotein during hypercholesterolemia as this enzyme is essential for T3 production, which further has a vital role in the maintenance of lipid metabolism.

Ultrastructural changes of the external elastic lamina in experimental hypercholesterolemic porcine coronary arteries

The external elastic lamina (EEL) serves as a barrier for cells and macromolecules between the media and adventitia in the vascular wall. We evaluated the morphological changes and quantitative assessments of the EEL architecture in the coronary circulation of pigs fed with a high cholesterol diet. Confocal microscopy analysis of the EEL from hypercholesterolemic coronary arteries revealed an altered pattern characterized by fragmentation and disorganization of the EEL associated with an increase in the thickness. Computerized digital analysis of the images obtained by confocal scanning microscopy demonstrated that compared to normal coronary arteries, the EEL of hypercholesterolemic coronary arteries decreased in the percentage of their elastin content (30.80 +/- 1.64% vs. 47.85 +/- 1.82%, p = 0.001). The percentage of elastin content was negatively correlated with the vessel wall area (r = -0.82, p = 0.001). The immunoreactivity for matrix metalloproteinase-3 (MMP-3) increased in cholesterol-fed coronary arteries, predominantly in the neointima and adventitia. This study demonstrates that experimental hypercholesterolemia induced ultrastructural changes of the EEL in coronary circulation. The EEL may also be an atherosclerosis-prone area compared with the intima. The EEL may play an important role in the development of structural changes which characterizes the early phase of coronary atherosclerosis and vascular remodeling.