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Purpose: The deiodinases activate or inactivate the thyroid hormones (TH) in virtually all tissues in both physiological and pathological conditions. The three deiodinases, DIO1, DIO2, and DIO3, have different catalytic functions and regulate TH tissue distribution. The aim of the present study was to evaluate the modulation of gene expression of the deiodinases and TH transporters and protein levels of DIO1 in parietal and frontal areas of cerebral cortex of spontaneously hypertensive rats (SHRs), after two successive mandibular extensions (ME). Methods: ME was performed on anesthetized rats by a dilatator appropriately designed and real-time PCR and western blotting techniques were employed for gene expression and protein level study. Results: Mean blood pressure (MBP) significantly decreased in 2ME-treated rats when compared to sham-operated rats (p< 0.001) and this decrease lasted for the entire observation period. In gene expression analysis, in 2ME-treated rats we did not observe any significant variation of DIO1 and DIO3 with respect to the sham-operated rats. Differently, DIO2 gene expression significantly increased in frontal area of 2ME-treated rats, with respect to sham-operated rats (p< 0.01). Furthermore, in parietal area, protein levels of DIO1 in 2ME-treated rats were significantly higher than in sham-operated rats (p< 0.01). Moreover MCT8 and OATP1C1 both resulted significantly higher (p< 0.05 and p< 0.001) in sham frontal cortex. Conclusion: In summary, our data on SHRs, while confirming the hypotensive effect of two MEs, show that the treatment also solicits the three deiodinases production in the cerebral cortex.

Oxidative stress has a pivotal and widely described role in the onset and progression of atherosclerotic plaque and cardiovascular disease. Many oxidative stress-related biomarkers can be measured in biological samples; however, there are still many aspects that limit the adoption of oxidative stress assessment in clinical laboratory practice. Here, we report an overview of the different sources and main common oxidative stress biomarkers relevant for cardiovascular physiopathology, describing in detail a recently proposed lipidomic assay for ceramide assessment, as a promising future development in oxidative stress evaluation among the many available redox-related tests.

The cardiovascular system is an important target for thyroid hormones (THs). Until recently, our understanding of the biological role of THs has been largely based on a catalog of effects observed in excess or deficiency of THs. In the last decades, however, some important progress has been done in defining the molecular and biochemical basis of thyroid hormone action at the cellular and nuclear level. Most of the molecular and cellular mechanisms responsible for the effects of THs on the heart have been clarified, whereas few data are available about the mechanisms of action of THs on the vasculature. Data reported so far describe the thyroid hormone effects on the vascular system as indirect consequences of thermogenic or hemodynamic derangements. The aim of this review is to focus on the direct role of THs in the vascular system, to analyze the main factors involved in this regulatory process, to evaluate the causes of imbalance, their relationships to some pathophysiological conditions, and, finally, to hypothesize effective therapeutic approaches. Our review considers data on the molecular and biochemical properties of iodothyronine deiodinases, with particular attention to D2, the enzyme for the local conversion of the precursor thyroxine (T4) into the biologically active triiodothyronine (T3). We summarize data on the deiodinase tissue distribution, subcellular localization, topology and structure-activity relationships. We also discuss the physiological role of deiodinases and their involvement in the THmediated regulation of vascular function.

We have developed a sensitive, specific and reproducible radioimmunoassay (RIA) for measurement of human type I monodeiodinase (5'-DI) protein. Anti-5'-DI antibody was produced by immunization of rabbits with a conjugate of bovine serum albumin and a 16 amino acid synthetic peptide, corresponding to a portion of the carboxy-terminal region of the human 5'-DI (PI-99). In a final dilution of 1:500, our anti-5'-DI antibody bound about 30%-35% of a tracer amount of 125I-PI-99. The detection threshold of the RIA approximated 0.4 pmol PI-99 or an equivalent amount of 0.4 pmol 5'-DI. The coefficient of variation averaged 5% within an assay and 14% between assays. Dose-response curves of tissue proteins were essentially parallel to that of PI-99. In a total number of 35 normal human tissue samples, the mean (± standard deviation [SD], picomole per milligram of protein [pmol]) 5'-DI content was 25 ± 6.7 in kidney, it was significantly lower (p< 0.05) in liver at 3.9 ± 1.1, 2.8 ± 0.8 in intestine, 2.3 ± 0.98 in adrenal, 4.2 ± 2.5 in skeletal muscle, 3.8 ± 1.4 in heart and 2.6 ± 2.4 in thyroid; it was 1.4 ± 0.3 in Graves' thyroid. Our data suggest that (1) 5'-DI is distributed widely among human tissues; (2) kidney is the tissue most enriched with 5'-DI; (3) 5'-DI content in the thyroid is not increased in Graves' disease.