Thyrotropin-releasing hormone in cardiovascular pathophysiology

Garcı́a, Silvia; Pirola, Carlos José

doi:10.1016/j.regpep.2005.01.002

Cited by 16 publications

(13 citation statements)

References 72 publications

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“…In fact, in almost all of our protocols, we measured thyroid hormones [T 3 and thyroxine (T 4 )] and TSH, confirming these results (6). Indeed, other laboratories have demonstrated the existence of different pools of TRH neurons around the central nervous system, indicating that there are many TRH-induced effects that do not involve TSH stimuli.…”

supporting

confidence: 85%

“…To confirm the specificity of TRH overexpression, prepro-TRH gene expression was evaluated in other heart tissues of the same animals such as the diencephalon, because it is known that the central TRH system participates not only in the endocrine system but also in cardiovascular regulation (6), as well as in the pancreas, where the tripeptide has also been found (19). No differences were observed between the two groups, indicating the specificity of the treatment in inducing LV TRH overexpression [diencephalic preproTRH: 100 Ϯ 17 arbitrary units in the PCMV-Con group vs. 142 Ϯ 22 arbitrary units in the PCMV-TRH group and pancreatic preproTRH: 100 Ϯ 11 arbitrary units in the PCMV-Con group vs. 90 ϩ 25 arbitrary units in the PCMV-TRH group, not significant (NS)].…”

Section: Resultsmentioning

confidence: 99%

“…The residue was dissolved in the appropriate buffer for the measurement of TRH-like immunoreactivity by RIA or the mobile phase for the identification of authentic TRH by HPLC. This procedure and the RIA for TRH have been previously reported in detail (6).…”

Section: Methodsmentioning

confidence: 99%

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Thyrotropin-releasing hormone overexpression induces structural changes of the left ventricle in the normal rat heart

Schuman

Diaz

Landa³

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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Schuman ML, Peres Diaz LS, Landa MS, Toblli JE, Cao G, Alvarez AL, Finkielman S, Pirola CJ, García SI. Thyrotropin-releasing hormone overexpression induces structural changes of the left ventricle in the normal rat heart. Am J Physiol Heart Circ Physiol 307: H1667-H1674, 2014. First published October 3, 2014; doi:10.1152/ajpheart.00494.2014.-Thyrotropin-releasing hormone (TRH) hyperactivity has been observed in the left ventricle of spontaneously hypertensive rats. Its long-term inhibition suppresses the development of hypertrophy, specifically preventing fibrosis. The presence of diverse systemic abnormalities in spontaneously hypertensive rat hearts has raised the question of whether specific TRH overexpression might be capable of inducing structural changes in favor of the hypertrophic phenotype in normal rat hearts. We produced TRH overexpression in normal rats by injecting into their left ventricular wall a plasmid driving expression of the preproTRH gene (PCMV-TRH). TRH content and expression of preproTRH, collagen type III, brain natriuretic peptide, ␤-myosin heavy chain, Bax-toBcl-2 ratio, and caspase-3 were measured. The overexpression maneuver was a success, as we found a significant increase in both tripeptide and preproTRH mRNA levels in the PCMV-TRH group compared with the control group. Immunohistochemical staining against TRH showed markedly positive brown signals only in the PCMV-TRH group. TRH overexpression induced a significant increase in fibrosis, evident in the increase of collagen type III expression accompanied by a significant increase in extracellular matrix expansion. We found a significant increase in brain natriuretic peptide and ␤-myosin heavy chain expression (recognized markers of hypertrophy). Moreover, TRH overexpression induced a slight but significant increase in myocyte diameter, indicating the onset of cell hypertrophy. We confirmed the data "in vitro" using primary cardiac cell cultures (fibroblasts and myocytes). In conclusion, these results show that a specific TRH increase in the left ventricle induced structural changes in the normal heart, thus making the cardiac TRH system a promising therapeutic target.heart; rat; thyrotropin-releasing hormone; fibrosis THYROTROPIN-RELEASING HORMONE (TRH), a small neuropeptide (p-Glu-His-Pro-NH 2 ) initially identified in the hypothalamus, is amply distributed in the central nervous system (17) and in other extra neural tissues (4). TRH also acts on the cardiovascular system of rodents, increasing blood pressure, heart rate, and contractility after its intracerebroventricular or intravenous administration (15). The hypertensive effect of TRH seems to be independent from the TRH-thyroid stimulating hormone (TSH)-triiodothyronine (T 3 ) system. In fact, in almost all of our protocols, we measured thyroid hormones [T 3 and thyroxine (T 4 )] and TSH, confirming these results (6). Indeed, other laboratories have demonstrated the existence of different pools of TRH neurons around the central nervous system, indicating that there are many T...

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confidence: 85%

Section: Resultsmentioning

confidence: 99%

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Thyrotropin-releasing hormone overexpression induces structural changes of the left ventricle in the normal rat heart

Schuman

Diaz

Landa³

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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“…To confirm the specificity of the in vivo iRNA treatment, we decided to quantify preproTRH gene expression on the diencephalum, because it is known that the TRH system participates not only in the endocrine system but also in cardiovascular regulation 12 and in other extraneuronal tissues where the tripeptide has been found. 13 We also evaluated the thyroid status in both groups of animals.…”

Section: Lv-trh Long-term Inhibition By Intracardiac Irna Treatmentmentioning

confidence: 99%

Cardiac Thyrotropin-Releasing Hormone Mediates Left Ventricular Hypertrophy in Spontaneously Hypertensive Rats

Schuman

Landa²,

Toblli³

et al. 2011

Hypertension

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Abstract-Local thyrotropin-releasing hormone (TRH) may be involved in cardiac pathophysiology, but its role in left ventricular hypertrophy (LVH) is still unknown. We studied whether local TRH is involved in LVH of spontaneously hypertensive rats (SHR) by investigating TRH expression and its long-term inhibition by interference RNA (TRH-iRNA) during LVH development at 2 stages (prehypertrophy and hypertrophy). SHR and their control rats (WKY) were compared. Cardiac hypertrophy was expressed as heart/total body weight (HW/BW) ratio. TRH content (radioimmuno assay), preproTRH, TRH receptor type I, brain natriuretic peptide (BNP), and collagen mRNA expressions (real-time polymerase chain reaction) were measured. For long-term inhibition of TRH, TRH-iRNA was injected into the left ventricle (LV) wall for 8 weeks. Hearts were processed for morphometric studies and immunohistochemical analysis using antibodies against ␣-smooth muscle actin and collagen type III. LV preproTRHmRNA abundance was similar in both strains at 7 weeks of age. At the hypertrophic stage (18 weeks old), however, there was a 15-fold increase in SHR versus WKY, consistent with a significant increase in tripeptide levels and the expression of its receptor. Specific LV-TRH inhibition at the prehypertensive stage with TRH-iRNA, which decreased Ͼ50% preproTRH expression and tripeptide levels, prevented LVH development as shown by the normal HW/BW ratio observed in TRH-iRNA-treated SHR. In addition, TRH-iRNA impeded the increase in BNP and type III collagen expressions and prevented the increase in cardiomyocyte diameter evident in mismatch iRNA-treated adult SHR. These results show for the first time that the cardiac TRH system is involved in the development of LVH in SHR. (Hypertension. 2011;57:103-109.) • Online Data SupplementKey Words: TRH Ⅲ cardiac hypertrophy Ⅲ rat Ⅲ SHR Ⅲ interference RNA T hyrotropin-releasing hormone (TRH), a small neuropeptide (p-Glu-His-Pro-NH2) initially identified in the hypothalamus, is amply distributed in the central nervous system 1 and in other extraneural tissues 2 and has been shown to have central and peripheral biological effects independent of thyroid hormone production. 3 TRH also acts on the cardiovascular system of rodents. 4,5 Many groups have identified preproTRH-mRNA by Northern blot analysis and RNAse protection assay in rat cardiac tissues and have referred the presence of specific type I TRH receptors (TRH-R1) in ventricles, establishing that a TRH system is present in the rat heart. 6 -8 In contrast to the hypothalamic TRH system, cardiac preproTRH-mRNA may be augmented by glucocorticoids and by testosterone but may not be regulated by T 3 . 8 In addition, Hasegawa et al 9 reported for the first time an inotropic effect of TRH on the guinea pig myocardium, implying that this effect could be mediated by an increase in a slow inward Ca 2ϩ current. Furthermore, Socci et al 7 found similar results and reported that TRH modulates cardiac contractility of isolated rat hearts as an autocrine factor in a conce...

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“…One of them, the CLOCK gene, a master regulator of circadian function associated with MS in humans as already mentioned (29,30) and rodent studies (31), was connected to corticotropin releasing hormone and proopiomelanocortin-related nodes. The second one, the SLC7A5-related nodes, predicted thyrotropin-releasing hormone, which was associated with hypertension, obesity-related hypertension, and control of body weight in rodents (32,33) and in humans (34).…”

Section: Reviewmentioning

confidence: 99%

Fetal metabolic programming and epigenetic modifications: a systems biology approach

et al. 2013

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A growing body of evidence supports the notion that epigenetic changes such as DNA methylation and histone modifications, both involving chromatin remodeling, contribute to fetal metabolic programming. We use a combination of gene-protein enrichment analysis resources along with functional annotations and protein interaction networks for an integrative approach to understanding the mechanisms underlying fetal metabolic programming. systems biology approaches suggested that fetal adaptation to an impaired nutritional environment presumes profound changes in gene expression that involve regulation of tissue-specific patterns of methylated cytosine residues, modulation of the histone acetylation-deacetylation switch, cell differentiation, and stem cell pluripotency. The hypothalamus and the liver seem to be differently involved. In addition, new putative explanations have emerged about the question of whether in utero overnutrition modulates fetal metabolic programming in the same fashion as that of a maternal environment of undernutrition, suggesting that the mechanisms behind these two fetal nutritional imbalances are different. In conclusion, intrauterine growth restriction is most likely to be associated with the induction of persistent changes in tissue structure and functionality. conversely, a maternal obesogenic environment is most probably associated with metabolic reprogramming of glucose and lipid metabolism, as well as future risk of metabolic syndrome (Ms), fatty liver, and insulin (INs) resistance.L arge amounts of epidemiological data showed that impaired intrauterine growth and adult metabolic and cardiovascular disorders, including coronary heart disease, type 2 diabetes, and insulin (INS) resistance, are strongly associated (1-4). Actually, the first exploration of a putative connection between environmental influence in early life and the risk of cardiovascular disease in adulthood was done by David Barker and coworkers, who followed-up a cohort of 499 men and women born in Preston (Lancashire, UK) during 1935-1943, and observed that as adults the highest blood pressures occurred in people who had been small babies with large placentas (5).Of note, the concept of a relationship between birth weight and adult chronic diseases initially described in low-birthweight babies was further extended to large-for-gestational age (LGA) babies, and the term of inappropriate gestational weight gained acceptance to better illustrate changes in earlylife metabolic environment that contribute to the risk of metabolic syndrome (MS) in adulthood (6).Barker and Hales also provided the initial answer to the question of how birth weight and adult chronic diseases are connected. They explained that fetuses adapt to an impaired supply of nutrients by changing their physiology and metabolism, and altering the sensitivity of tissues causes an abnormal structure and function in adult life; thereby, they formulated the "thrifty phenotype hypothesis" (7,8).Altogether, the above-mentioned clinico-epidemiological evidence str...

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Thyrotropin-releasing hormone in cardiovascular pathophysiology

Cited by 16 publications

References 72 publications

Thyrotropin-releasing hormone overexpression induces structural changes of the left ventricle in the normal rat heart

Thyrotropin-releasing hormone overexpression induces structural changes of the left ventricle in the normal rat heart

Cardiac Thyrotropin-Releasing Hormone Mediates Left Ventricular Hypertrophy in Spontaneously Hypertensive Rats

Fetal metabolic programming and epigenetic modifications: a systems biology approach

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