Transcriptome of hypertension-induced left ventricular hypertrophy and its regression by antihypertensive therapies

Gállego-Delgado, Julio; Connolly, Susan; Lázaro, Alberto; Sadlier, Denise; Kieran, Niamh E.; Sugrue, D.; Doran, Peter; Brady, Hugh R.; Osende, Julio I.; Egido, Jesús

doi:10.1038/hr.2009.27

Cited by 12 publications

(10 citation statements)

References 57 publications

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“…In this regard, several key regulators of muscle cell growth and proliferation (MAP3K7IP2, MSTN, PHB2, APOBEC3F) and gene expression (PTPLAD1, JMJD1C, CEP290) are differentially expressed between LV and RV piglet myocardium that may be relevant to intrinsic differences [31] that can regulate the chamber-dependent response of ventricular myocardium to workload. Interestingly, transition from “early” to “late” hypertension-induced hypertrophy in young adult rats is associated with predominant changes in expression of cell growth/proliferation and signal transduction factors [32]. …”

Section: Discussionmentioning

confidence: 99%

Identification of Candidate Genes Potentially Relevant to Chamber-Specific Remodeling in Postnatal Ventricular Myocardium

Torrado

Iglesias

Nespereira

et al. 2010

Journal of Biomedicine and Biotechnology

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Molecular predisposition of postnatal ventricular myocardium to chamber-dependent (concentric or eccentric) remodeling remains largely elusive. To this end, we compared gene expression in the left (LV) versus right ventricle (RV) in newborn piglets, using a differential display reverse transcription-PCR (DDRT-PCR) technique. Out of more than 5600 DDRT-PCR bands, a total of 153 bands were identified as being differentially displayed. Of these, 96 bands were enriched in the LV, whereas the remaining 57 bands were predominant in the RV. The transcripts, displaying over twofold LV-RV expression differences, were sequenced and identified by BLAST comparison to known mRNA sequences. Among the genes, whose expression was not previously recognized as being chamber-dependent, we identified a small cohort of key regulators of muscle cell growth/proliferation (MAP3K7IP2, MSTN, PHB2, APOBEC3F) and gene expression (PTPLAD1, JMJD1C, CEP290), which may be relevant to the chamber-dependent predisposition of ventricular myocardium to respond differentially to pressure (LV) and volume (RV) overloads after birth. In addition, our data demonstrate chamber-dependent alterations in expression of as yet uncharacterized novel genes, which may also be suitable candidates for association studies in animal models of LV/RV hypertrophy.

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Section: Discussionmentioning

confidence: 99%

Identification of Candidate Genes Potentially Relevant to Chamber-Specific Remodeling in Postnatal Ventricular Myocardium

Torrado

Iglesias

Nespereira

et al. 2010

Journal of Biomedicine and Biotechnology

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“…9, 19 Our data confirmed that all patients’ RV functional parameters improved after LT. Of note, RV hypertrophy was also resolved in all patients, in which mechanism can be seen in the reversibility of LV hypertrophy in hypertensive patients under antihypertensive therapies. 20, 21 Meanwhile, pre-existing LV dysfunction is a primary determinant for eliminating LT candidacy at many centers. 9, 19 In our cohort, all patients had a preserved LV function before LT (mean LVEF 58.9±6.0%), which did not change after LT (57.9±9.7%).…”

Section: Discussionmentioning

confidence: 99%

Left and Right Ventricular Functional Dynamics Determined by Echocardiograms Before and After Lung Transplantation

Kato

Armstrong

Schulze

et al. 2015

The American Journal of Cardiology

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Impaired cardiac function is considered a contraindication for lung transplantation (LT). Since right ventricular (RV) function is expected to improve after LT, poor left ventricular (LV) function is often the determinant for LT eligibility. However, the changes in cardiac function before and after LT have not yet been elucidated. Therefore, we reviewed echocardiograms obtained from 67 recipients before and after LT. In a subset of 49 patients, both RV and LV longitudinal strains based on 2D speckle tracking echocardiography were analyzed. The cardiopulmonary exercise tests were also reviewed. All patients showed significant improvements in their exercise capacity after LT. RV-echo parameters improved in all patients following LT (RV fractional area change: 36.7±5.6 to 41.5±2.7%, RV strain: −15.5±2.9 to −18.0±2.1%, RV E/E’: 8.4±1.8 to 7.7±1.8; all p<0.05). Overall, the LV ejection fraction (LVEF) did not change (58.7±6.0 to 57.5±9.7%, p=0.385); however, 20 patients (30%) showed more than a 10% decrease in LVEF after LT (61.5±6.1 to 47.3±4.2%, p<0.001), and an increase in LV E/E’ (11.8±1.8 to 12.9±2.2, p=0.049). Multivariate logistic regression analysis revealed that pre-LT LV E/E’ was associated with decrease in LVEF after LT [odds ratio (OR) 1.381, 95%CI (confidential interval) 1.010–1.947, p=0.043]. Furthermore, patients with strain data showed lower pre-LT LV strain was independently associated with LVEF decrease after LT (OR 1.293, 95%CI 1.088–1.614, p=0.002). While RV function improves after LT, LV systolic and diastolic functions deteriorate in a sizable proportion of patients. Impaired LV diastolic function before transplant appears to increase the risk of LVEF deterioration after LT.

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“…Of particular interest was the analysis of unique transcripts arising from novel exons, splice variants and alternate sites of initiation/termination otherwise absent from mainstream genome databases . The transcriptome of left ventricular hypertrophy has been investigated, observing close to 300 transcripts altered during early stages of disease progression . This study also investigated the modulation of the transcriptome in response to pharmacological intervention and observed that whilst the disease showed regression, there was an absence of significant changes , indicating a level of control beyond the transcriptome.…”

Section: Cvd and The Genomementioning

confidence: 99%

“…The transcriptome of left ventricular hypertrophy has been investigated, observing close to 300 transcripts altered during early stages of disease progression . This study also investigated the modulation of the transcriptome in response to pharmacological intervention and observed that whilst the disease showed regression, there was an absence of significant changes , indicating a level of control beyond the transcriptome. As discussed above, if poor adaptation to changing conditions is the prelude to disease, proteins, as mediators of cellular function, also play an integral role in the cellular phenotype.…”

Section: Cvd and The Genomementioning

confidence: 99%

The role of post‐translational modifications in acute and chronic cardiovascular disease

Smith

White

2014

Proteomics Clinical Apps

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Cardiovascular disease (CVD) in one of the leading causes of mortality and morbidity worldwide, accounting for both primary diseases of the heart and vasculature and arising as a co-morbidity with numerous pathologies, including type 2 diabetes mellitus (T2DM). There has been significant emphasis on the role of the genome in CVD, aiding in the definition of 'at-risk' patients. The extent of disease penetrance however, can be influenced by environmental factors that are not detectable by investigating the genome alone. By targeting the transcriptome in response to CVD, the interplay between genome and environment is more apparent, however this implies the level of protein expression without reference to proteolytic turnover, or potentially more importantly, without defining the role of PTMs in the development of disease. Here, we discuss the role of both brief and irreversible PTMs in the setting of myocardial ischemia/reperfusion injury. Key proteins involved in calcium regulation have been observed as differentially modified by phosphorylation/O-GlcNAcylation or phosphorylation/redox modifications, with the level of interplay dependent on the physiological or pathophysiological state. The ability to modify crucial sites to produce the desired functional output is modulated by the presence of other PTMs as exemplified in the T2DM heart, where hyperglycemia results in aberrant O-GlcNAcylation and advanced glycation end products. By using the signalling events predicted to be critical to post-conditioning, an intervention with great promise for the cardioprotection of the ischemia/reperfusion injured heart, as an example, we discuss the level of PTMs and their interplay. The inability of post-conditioning to protect the diabetic heart may be regulated by aberrant PTMs influencing those sites necessary for protection.

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Transcriptome of hypertension-induced left ventricular hypertrophy and its regression by antihypertensive therapies

Cited by 12 publications

References 57 publications

Identification of Candidate Genes Potentially Relevant to Chamber-Specific Remodeling in Postnatal Ventricular Myocardium

Identification of Candidate Genes Potentially Relevant to Chamber-Specific Remodeling in Postnatal Ventricular Myocardium

Left and Right Ventricular Functional Dynamics Determined by Echocardiograms Before and After Lung Transplantation

The role of post‐translational modifications in acute and chronic cardiovascular disease

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