Gestational Protein Restriction Increases Cardiac Connexin 43 mRNA levels in male adult rat offspring

Abstract

BackgroundThe dietary limitation during pregnancy influences the growth and development of the fetus and offspring and their health into adult life. The mechanisms underlying the adverse effects of gestational protein restriction (GPR) in the development of the offspring hearts are not well understood.ObjectivesThe aim of this study was to evaluate the effects of GPR on cardiac structure in male rat offspring at day 60 after birth (d60).MethodsPregnant Wistar rats were fed a normal-protein (NP, 17% casein) or low-protein (LP, 6% casein) diet. Blood pressure (BP) values from 60-day-old male offspring were measured by an indirect tail-cuff method using an electro sphygmomanometer. Hearts (d60) were collected for assessment of connexin 43 (Cx43) mRNA expression and morphological and morphometric analysis.ResultsLP offspring showed no difference in body weight, although they were born lighter than NP offspring. BP levels were significantly higher in the LP group. We observed a significant increase in the area occupied by collagen fibers, a decrease in the number of cardiomyocytes by 104 µm2, and an increase in cardiomyocyte area associated with an increased Cx43 expression.ConclusionGPR changes myocardial levels of Cx43 mRNA in male young adult rats, suggesting that this mechanism aims to compensate the fibrotic process by the accumulation of collagen fibers in the heart interstitium.

Protein Restriction in the Peri-Pubertal Period Induces Autonomic Dysfunction and Cardiac and Vascular Structural Changes in Adult Rats

“…This is the first demonstration of adult neurogenic hypertension programmed in the peri-pubertal period, while other studies have addressed the effect of low protein diet on blood pressure just after the exposure to the insult ( Loss et al, 2007 ; Penitente et al, 2007 ; Del Carmen Miñana-Solis and Escobar, 2008 ; Martins et al, 2011 ; Murca et al, 2012 ; Gomide et al, 2013 ; Penitente et al, 2014 ; Cappelli et al, 2018 ). In the context of DOHaD concept the studies have explored an earlier susceptible window of development, the peri-natal period ( Latorraca et al, 1998 ; De Oliveira et al, 2011 ; De Brito Alves et al, 2014 ; De Oliveira et al, 2014 ; Nascimento et al, 2014 ; Barros et al, 2015 ; De Oliveira et al, 2016 ; Ferreira et al, 2016 ; Paulino-Silva and Costa-Silva, 2016 ; Rossini et al, 2017 ; Barros et al, 2018 ; Martins et al, 2018 ; Assalin et al, 2019 ; Ferreira et al, 2019 ). The exact stimulus to the neurogenic hypertension is difficult to determine as the LP animals were hypophagic during the period of protein restriction, which also induced a caloric-restriction in peri-puberty, and a critical window of development ( De Oliveira et al, 2013 ; De Oliveira et al, 2018 ).…”

“…A similar profile was observed by Ferreira et al (2019) , who showed that carbonylated proteins and SOD were decreased, while malonildialdehyde, a lipid peroxidation marker, and glutathione transferase enzyme were increased in the brainstem in PN150 rats exposed to perinatal protein restriction ( Ferreira et al, 2019 ). Oxidative stress is a mechanism involved in the sympathetic arousal generated from the brainstem and resulting in cardiac remodeling ( Rossini et al, 2017 ; Assalin et al, 2019 ). Therefore, the present disorganization of the redox state must be better explored to assess its role as a mediator of the observed dysfunctions.…”

“…The increase in the cardiomyocyte diameter and interstitial fibrosis in relatively young animals exposed to the peri-pubertal protein restriction, and in the absence of perivascular fibrosis observed, suggests that we are observing the beginning of a cardiac remodeling process following elevated blood pressure and ANS dysregulation. Programming studies with LP diet during pregnancy point to a more advanced cardiac morphological disorganization at PN60 or PN112, including collagen deposition in the heart ( Rossini et al, 2017 ; Assalin et al, 2019 ), decreased number of cardiomyocytes ( Silva et al, 2013 ; Rossini et al, 2017 ; Assalin et al, 2019 ), and changes in heart expression of miRNA related to cardiac structure and function ( Assalin et al, 2019 ). The difference in the cardiac histological profile observed between perinatal insult versus the insult during peri-puberty may indicate that peri-pubertal period is a less vulnerable period in terms of disease acquisition, or it may simply represent a rightward shift in the curve.…”

“…Experimental programming models of malnutrition or nutritional imbalance during the perinatal period show that arterial hypertension may be associated with increase in vascular sympathetic tone ( Mizuno et al, 2013 ; Prior et al, 2014 ; Barros et al, 2015 ; Paulino-Silva and Costa-Silva, 2016 ; Lim et al, 2021 ) as well as redox disorganization in the brainstem ( Ferreira et al, 2016 ; Barrand et al, 2017 ; Ferreira et al, 2019 ), and heart ( Nascimento et al, 2014 ). Furthermore, the hypertension may trigger a cardiac compensatory response, leading to cardiomyocyte hypertrophy, and greater collagen deposition ( Rossini et al, 2017 ; De Jong et al, 2018 ; Assalin et al, 2019 ).…”

Role of moxifloxacin-dexamethasone in cardiac histomorphometric findings among Wistar rats from infected mothers

“…In this research, the histomorphometric measurements were performed using the Image J 1.51, Java 1.8.0_101 (64-bit) digital image analysis software. This program is widely used in scientific research involving quantification and analysis of images [5][6][7][8][9][10] , with programming platform based on the Java language. In a systematic way, all the photomicrographs were processed according to the same algorithm.…”