Increased apoptosis in the heart of genetic hypertension, associated with increased fibroblasts

Liu, James J.; Peng, Lihua; Bradley, Christopher; Zulli, Anthony; Shen, Jun; Buxton, Brian F.

doi:10.1016/s0008-6363(99)00382-x

Cited by 53 publications

(43 citation statements)

References 10 publications

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“…Interestingly, an increased cell death occurs before ABP increase in the SHR heart, as reported by Liu et al 17 Additional studies using cardiac cell cultures, as we found specific type I TRH receptor expression in cultured neonatal cardiomyocytes and fibroblasts (unpublished results), would be necessary to elucidate the mechanism by which TRH induces the development of LVH. Figure 5.…”

Section: Perspectivessupporting

confidence: 73%

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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Section: Perspectivessupporting

confidence: 73%

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

Schuman

Landa²,

Toblli³

et al. 2011

Hypertension

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“…In addition, we found the number of apoptotic nuclei/mm 2 in the TG to be more than that of the SD in both the SA and the AV nodes in all age-groups (two-day, one-week and two-week). The results correspond to the work of Liu et al,15 who demonstrated that there is increased apoptosis in the heart of spontaneously hypertensive rats (SHR).…”

Section: Discussionsupporting

confidence: 91%

Angiotensin II may mediate apoptosis via AT1-receptors in the rat cardiac conduction system

Vongvatcharanon

Radenahmad

et al. 2004

J Renin Angiotensin Aldosterone Syst

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IntroductionApoptosis and angiotensin II (Ang II) have been suggested as possible causes of arrhythmias. In addition, Ang II via Ang II type I (AT 1 -) receptors, has been demonstrated to induce cardiomyocyte apoptosis. The transgenic m(Ren-2)27 (TG) rat carries the additional Ren-2 gene, the expression of which results in an increase in cardiac Ang II, thus potentially affecting the cell growth/death equilibrium. In this study we have investigated the effect of Ang II, via AT 1 -receptors, on mediating apoptosis in a cardiac conduction system (SA node and AV nodes). Materials and methodsHeart sections from male two-day, one-week and two-week TG and Sprague-Dawley (SD) rats were stained with Masson Trichrome to localise the SA and AV nodes. The sections containing SA or AV nodes were processed for quantitation of apoptotic nuclei and AT 1 -receptors. ResultsThe number of apoptotic nuclei/mm 2 in the SA and AV nodes were found to decrease from two days to two weeks in both the TG and the SD rats, and the number of apoptotic nuclei/mm 2 in the TG groups was significantly higher than that of the SD groups for all ages (p<0.05). The number of AT 1 -receptors/mm 2 in the SA node were found to decrease with increasing age, whereas the number of AT 1 -receptors/mm 2 in the AV node was increased in both TG and SD rats and the number of AT 1 -receptors/mm 2 in the three TG groups was significantly more than that of the three SD groups (p<0.05). Discussion and conclusionAs a consequence of the additional renin gene in the TG rats, which results in the alteration of the local reninangiotensin system, the numbers of AT 1 -receptors/mm 2 and apoptotic nuclei/mm 2 are increased. The number of apoptotic nuclei/mm 2 and AT 1 -receptors/mm 2 in the SA node decrease with maturation, whereas, the number of AT 1 -receptors in the AV node increase. Thus, there may be a correlation between Ang II and apoptosis in the SA node, which does not appear to be present in the AV node.

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“…Z-VAD-FMK, a pancaspase inhibitor (36)(37)(38)(39)(40)(41)(42), can inhibit cell death in response to mechanical injury. Interestingly, our results showed that Z-VAD-FMK could inhibit chondrocyte death more effectively in chondroitinase ABC-treated explants than in control explants.…”

Section: Discussionmentioning

confidence: 99%

The effect of glycosaminoglycan loss on chondrocyte viability: A study on porcine cartilage explants

Otsuki¹,

Brinson²,

Creighton³

et al. 2008

Arthritis & Rheumatism

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Objective. Loss of glycosaminoglycan (GAG) is an early event in osteoarthritis. Recent findings showed increased cell death in arthritic cartilage and linkage with extracellular matrix degradation. The aim of this study was to analyze the direct effect of GAG loss on chondrocyte survival and cell death following mechanical injury.Methods. In full-thickness cartilage explants from porcine knee joints, GAG was depleted by digestion with chondroitinase ABC. Explants were subjected to single-impact mechanical injury. Cell viability and the types of cell death were analyzed by Live/Dead cell assay, staining for active caspase 3, and sensitivity to caspase inhibitor.Results. GAG depletion did not directly lead to increased cell death. In chondroitinase ABC-treated explants, but not in control explants, mechanical injury caused an immediate reduction in cell viability (from 84.6% to 71.0%); the reduction was prominent in the superficial zone. This immediate cell death was not inhibited by the pancaspase inhibitor Z-VAD-FMK, suggesting cell necrosis. During subsequent culture, viability in these explants decreased further, to 50.5% on day 3. The second wave of cell death was reduced by the addition of Z-VAD-FMK in chondroitinase ABC-treated explants and was also associated with activation of caspase 3, suggesting apoptotic mechanisms of cell death.Conclusion. These results indicate that GAG loss alone does not directly lead to chondrocyte death. In response to mechanical injury, there is an immediate induction of necrotic cell death that is seen only in GAG-depleted explants and primarily in the superficial zone. During subsequent culture, cell death spreads via apoptotic mechanisms.

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Increased apoptosis in the heart of genetic hypertension, associated with increased fibroblasts

Cited by 53 publications

References 10 publications

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

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

Angiotensin II may mediate apoptosis via AT1-receptors in the rat cardiac conduction system

The effect of glycosaminoglycan loss on chondrocyte viability: A study on porcine cartilage explants

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