Browsing by Author "Nair, RR"

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    A positive association between cardiomyocyte volume and serum malondialdehyde levels
    (INTERNATIONAL JOURNAL OF CARDIOLOGY, 2007) Adiga, IK; Nair, RR
    Cardiac hypertrophy is the first visible sign of cardiac remodeling. Oxidative stress is implicated in the etiopathogenesis of cardiac hypertrophy. In vitro studies have shown that exposure of cardiomyocytes to free radical generators induce cell hypertrophy. However, there are no studies to show that in vivo redox status can influence cardiomyocyte growth. Blood samples were collected from healthy volunteers and serum lipid peroxidation was determined as a measure of oxidative stress. Cardiac myocytes cultured from newborn rat were exposed to serum samples. A significant correlation was observed between serum lipid peroxidation and cardiomyocyte volume, indicating that in vivo oxidative stress can act as an important co-factor in mediating the hypertrophic response. This experimental system also envisages a novel approach to identify patients prone to left ventricular remodeling and identification of Immoral factors mediating the changes. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
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    Age-dependent variation in contractility of adult cardiac myocytes
    (INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2001)
    This study was designed to examine the influence of the age of adults on the contractile characteristics of the myocardium and to ascertain whether the age dependent variation is related to variation in sarcolemmal calcium channels. Cardiomyocytes were isolated from 2, 6 and 12-month-old, male Sprague-Dawley rats and the extent and velocity of contraction were recorded as a function of change in cell length. Age dependent increase in cell length and sarcomere length was significant (P < 0.05). Extent of contraction increased with age and the velocities of contraction and relaxation normalized to total contraction decreased with age (P < 0.05). Sensitivity to the L-type channel antagonist (verapamil, 1 muM) and the T-type channel antagonist (nickel chloride, 40 muM) was significant in 6 and 12-month-old animals. This differential response to calcium channel antagonists suggests that the age-dependent variation in contractility may be mediated by the variation in the distribution/function of sarcolemmal calcium channels. (C) 2001 Elsevier Science Ltd. All rights reserved.
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    Alteration in cardiomyocyte mechanics by suboptimal levels of extracellular magnesium
    (BIOLOGICAL TRACE ELEMENT RESEARCH, 2000)
    The beneficial effects of magnesium supplementation in pathological situations is well known, but the myocardial response to a nominal decrease in the level of magnesium has received relatively little attention. Hypomagnesemia can occur as chronic or acute manifestation of physiological changes, pathological conditions, or pharmacological interventions. Experimental interest was focused on the mechanical changes in adult rat heart myocytes following variation in extracellular Mg2+. Isolated cells were exposed to different levels of extracellular Mg2+ and the amplitude and rate of contraction were measured as a function of change in cell length using a video-based edge-detection system. Investigations have revealed that variation in the level of Mg2+ within physiological limits leads to mechanical changes. A decrease in the level of extracellular Mg2+ was accompanied by a significant increase in contractile amplitude and decrease in the velocities of contraction and relaxation. The contractile amplitude measured as percentage shortening were 3.08 +/- 0.19%, 4.62 +/- 0.19% and 6.9 +/- 0.40%, respectively, on exposure to 1.8, 0.8, and 0.48 mM Mg, and the corresponding velocities of contraction and relaxation normalized to amplitude were 0.54 +/- 0.02, 0.40 +/- 0.03, 0.31 +/- 0.03 and 0.47 +/- 0.02, 0.35 +/- 0.02, 0.24 +/- 0.02. The variations in contractile parameters associated with the change in the level of Mg were statistically significant (p < 0.01). Variation in the contractile properties associated with change in extracellular Mg2+ may be effected by alteration in Ca2+ transients.
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    Alteration of myocardial mechanics in marginal magnesium deficiency
    (MAGNESIUM RESEARCH, 2002)
    Magnesium has attracted attention as an essential element with diverse roles in the regulation of cardiac contraction. Chronic suboptimal intake of the element results in hypomagnesaemia. Experimental and clinical studies indicate the possibility of a marginal decrease in myocardial magnesium compared to those with sufficient intake. Reduction in extracellular magnesium affects myocardial excitability and contractility predominantly, by modulation of the levels of other ions that have an influence on cardiac mechanics. Majority of the in vitro experiments in isolated ventricular tissue or myocytes record an inverse relation between Mg concentration and inotropic response, mediated probably by enhanced influx of Ca2+ promoting sarcoplasmic reticular Ca2+ release. Paradoxically myocardial contractility is usually compromised in animals on Mg deficient diet or on perfusion of whole heart with low Mg (< 0.5 mM) buffer. In the whole animal or organ, magnesium deficiency induced coronary vasospasm, defective energy metabolism and excessive free radical generation may be important variables acting in concert or independently to affect myocardial function. Electrical excitability is enhanced in magnesium deficiency, and arrhythmic changes are presumed to be mediated by disturbance in K+ homeostasis. Magnesium deficiency has not received the attention it deserves probably due to absence of clinical symptoms.Magnesium deficiency concomitant with stress may be of clinical significance, leading to arrhythmic, hemodynamic and ischaemic changes in the heart. Chronic magnesium deficiency is accompanied by increased free radical generation. Free radicals are known to influence myocardial excitability and contractility. Physiologic and pathologic stress also promotes free radical generation. The additive action of free radical generation in magnesium deficiency and any form of stress may be one of the reasons for enhanced sensitivity to stress in magnesium deficiency. Clinical and experimental data on the cardiac consequences of marginal magnesium deficiency being limited, a number of factors need experimental validation. For example- the extent of change in total and ionized magnesium in the serum and heart, mechanical response of the myocardium to decrease of total and ionized magnesium in the intra- and extracellular milieu; the extent of free radical generation in magnesium deficiency and the cardiac consequence; and also the additive effect of magnesium deficiency and different forms of stress.
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    Differential response of human cardiac stem cells and bone marrow mesenchymal stem cells to hypoxia-reoxygenation injury
    (MOLECULAR AND CELLULAR BIOCHEMISTRY, 2017) RajendranNair, DS; Karunakaran, J; Nair, RR
    Cardiosphere-derived cells (CDCs) and bone marrow mesenchymal stem cells (MSCs) are popularly used in stem cell therapy for myocardial regeneration. The cell type that survives and maintains stem cell characteristics in the adverse microenvironment following ischemia-reperfusion injury is presumed to be ideal for transplantation. The study was therefore aimed at identifying the cell type with relatively greater resistance to ischemia-reperfusion injury. CDCs were isolated from the right atrial appendage and MSCs from bone marrow of patients who underwent coronary artery bypass graft surgery. Ischemia-reperfusion injury was simulated in vitro by subjecting the cells to hypoxia (0.5% O-2) followed by reintroduction of oxygen (HR injury). Greater resistance of CDCs to HR injury was apparent from the decreased expression of senescence markers and lower proportion of apoptotic cells (one-sixth of that in MSCs). HR injury retarded cell cycle progression in MSCs. Consequent to HR injury, cell migration and secretion of stromal-derived growth factor were stimulated, significantly in CDCs. The differentiation to myocyte lineage and angiogenesis assessed by tube formation ability was better for CDCs. Release of vascular endothelial growth factor was relatively more in CDCs and was further stimulated by HR injury. Differentiation to osteogenic and angiogenic lineage was stimulated by HR injury in MSCs. Compared to MSCs, CDCs appear to be the cell of choice for promoting myocardial regeneration by virtue of its survival capacity in the event of ischemic insult along with higher proliferation rate, migration efficiency, release of growth factors with paracrine effects and differentiation to cardiac lineage.
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    Differential response of human cardiac stem cells and bone marrow mesenchymal stem cells to hypoxia-reoxygenation injury
    (Molecular and Cellular Biochemistry, 2017-03) Deepthi, RS; Jayakumar, K; Nair, RR
    Cardiosphere-derived cells (CDCs) and bone marrow mesenchymal stem cells (MSCs) are popularly used in stem cell therapy for myocardial regeneration. The cell type that survives and maintains stem cell characteristics in the adverse microenvironment following ischemia–reperfusion injury is presumed to be ideal for transplantation. The study was therefore aimed at identifying the cell type with relatively greater resistance to ischemia–reperfusion injury. CDCs were isolated from the right atrial appendage and MSCs from bone marrow of patients who underwent coronary artery bypass graft surgery. Ischemia–reperfusion injury was simulated in vitro by subjecting the cells to hypoxia (0.5% O2) followed by reintroduction of oxygen (HR injury). Greater resistance of CDCs to HR injury was apparent from the decreased expression of senescence markers and lower proportion of apoptotic cells (one-sixth of that in MSCs). HR injury retarded cell cycle progression in MSCs. Consequent to HR injury, cell migration and secretion of stromal-derived growth factor were stimulated, significantly in CDCs. The differentiation to myocyte lineage and angiogenesis assessed by tube formation ability was better for CDCs. Release of vascular endothelial growth factor was relatively more in CDCs and was further stimulated by HR injury. Differentiation to osteogenic and angiogenic lineage was stimulated by HR injury in MSCs. Compared to MSCs, CDCs appear to be the cell of choice for promoting myocardial regeneration by virtue of its survival capacity in the event of ischemic insult along with higher proliferation rate, migration efficiency, release of growth factors with paracrine effects and differentiation to cardiac lineage.
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    Genetic liability to epilepsy in Kerala State, India
    (EPILEPSY RESEARCH, 2004)
    Background: Familial clustering is common in epilepsies, but pedigree patterns suggest a multi-factorial inheritance. Genetic liability for multi-factorial inheritance is population specific and such data are not available for the population of Kerala or other states in south India.Objectives: In this study, we have attempted to determine the genetic liability to epilepsy based on an adult population of this state.Material and methods: Pedigrees were recorded for probands who reported to the Kerala Registry of Epilepsy and Pregnancy. In order to obtain a genetically matched sample for comparison and estimation of empiric risks, we have used the family history of the spouse except when the spouse was proband's relative. The ILAE criteria were followed for diagnosis and classification of epilepsy.Results: Data were collected on 18,419 family members of 505 probands with epilepsy (82 men and 423 women) and 10,231 family members of spouses (control). The frequency of epilepsy in first and second-degree relatives of the spouses was comparable to the population frequency (0.5%), justifying the use of this sample as control. Positive family history was observed in 22.2% of probands and 8.24% of controls (Odd's Ratio 3.2, 95% Confidence Interval 2.12-4.73). An affected first-degree relative was observed in 7.5% of probands. The corresponding figure for GE, LRE and other epileptic syndromes were 10.2%, 5.8% and 5.12%, respectively. The segregation ratio for Juvenile Myoclonic Epilepsy (JME) (1:19) was higher than that for other types of Generalized Epilepsy (GE) (1:24) and Localization Related Epilepsy (LRE) (1:52). Prevalence of epilepsy among the first-degree relatives (1.96%) was greater than the square root of the population frequency (0.51%) and was higher than that for second-degree (1.24%) and third-degree (0.64%) relatives for the probands. Probands had higher parental consanguinity (13.07%) compared to controls (6.64%). The above factors support a complex inheritance. Genetic liability to epilepsy (heritability) is greater for GE (0.6) and significantly higher for JME (0.7) compared to LRE (0.4). A limitation of this study is that the inferences are based on a predominantly adult female proband sample but no gender specific differences were identified.Conclusions: The observations of this study indicate complex inheritance and the liability values are useful for genetic counseling in the local population. Further studies involving more individuals from younger age group and male gender are envisaged. (C) 2004 Elsevier B.V. All rights reserved.
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    Ligand specific variation in cardiac response to stimulation of peroxisome proliferator-activated receptor-alpha in spontaneously hypertensive rat
    (MOLECULAR AND CELLULAR BIOCHEMISTRY, 2015) Ismael, S; Purushothaman, S; Harikrishnan, VS; Nair, RR
    Left ventricular hypertrophy (LVH) is an independent risk factor for cardiac failure. Reduction of LVH has beneficial effects on the heart. LVH is associated with shift in energy substrate preference from fatty acid to glucose, mediated by down regulation of peroxisome proliferator-activated receptor-alpha (PPAR-alpha). As long-term dependence on glucose can promote adverse cardiac remodeling, it was hypothesized that, prevention of metabolic shift by averting down regulation of PPAR-alpha can reduce cardiac remodeling in spontaneously hypertensive rat (SHR). Cardiac response to stimulation of PPAR-alpha presumably depends on the type of ligand used. Therefore, the study was carried out in SHR, using two different PPAR-alpha ligands. SHR were treated with either fenofibrate (100 mg/kg/day) or medium-chain triglyceride (MCT) Tricaprylin (5 % of diet) for 4 months. Expression of PPAR-alpha and medium-chain acylCoA dehydrogenase served as markers, for stimulation of PPAR-alpha. Both ligands stimulated PPAR-alpha. Decrease of blood pressure was observed only with fenofibrate. LVH was assessed from heart-weight/body weight ratio, histology and brain natriuretic peptide expression. As oxidative stress is linked with hypertrophy, serum and cardiac malondialdehyde and cardiac 3-nitrotyrosine levels were determined. Compared to untreated SHR, LVH and oxidative stress were lower on supplementation with MCT, but higher on treatment with fenofibrate. The observations indicate that reduction of blood pressure is not essentially accompanied by reduction of LVH, and that, progressive cardiac remodeling can be prevented with decrease in oxidative stress. Contrary to the notion that reactivation of PPAR-alpha is detrimental; the study substantiates that cardiac response to stimulation of PPAR-alpha is ligand specific.
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    Metabolic Modulation by Medium-Chain Triglycerides Reduces Oxidative Stress and Ameliorates CD36-Mediated Cardiac Remodeling in Spontaneously Hypertensive Rat in the Initial and Established Stages of Hypertrophy
    (J Cardiac failure, 2017-03) Ismael, S; Lakshmi, S; Remani, K; Nair, RR
    Background: Left ventricular hypertrophy (LVH) is characterized by a decrease in oxidation of longchain fatty acids, possibly mediated by reduced expression of the cell-surface protein cluster of differentiation 36 (CD36). Spontaneously hypertensive rats (SHRs) were therefore supplemented with medium-chain triglycerides (MCT), a substrate that bypasses CD36, based on the assumption that the metabolic modulation will ameliorate ventricular remodeling. Methods: The diet of 2-month-old and 6-month-old SHRs was supplemented with 5% MCT (Tricaprylin), for 4 months. Metabolic modulation was assessed by mRNA expression of peroxisome proliferator– activated receptor α and medium-chain acyl-CoA dehydrogenase. Blood pressure was measured noninvasively. LVH was assessed with the use of hypertrophy index, cardiomyocyte cross-sectional area, mRNA expression of B-type natriuretic peptide, cardiac fibrosis, and calcineurin-A levels. Oxidative stress indicators (cardiac malondialdehyde, protein carbonyl, and 3-nitrotyrosine levels), myocardial energy level (ATP, phosphocreatine), and lipid profile were determined. Results: Supplementation of MCT stimulated fatty acid oxidation in animals of both age groups, reduced hypertrophy and oxidative stress along with the maintenance of energy level. Blood pressure, body weight, and lipid profile were unaffected by the treatment. Conclusions: The results indicate that modulation of myocardial fatty acid metabolism by MCT prevents progressive cardiac remodeling in SHRs, possibly by maintenance of energy level and decrease in oxidative stress. (J Cardiac Fail 2017;23:240–251)
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    Mitoprotective antioxidant EUK- 134 stimulates fatty acid oxidation and prevents hypertrophy in H9C2 cells
    (Molecular and Cellular Biochemistry, 2016-09) Purushothaman, S; Nair, RR
    Oxidative stress is an important contributory factor for the development of cardiovascular diseases like hypertension-induced hypertrophy. Mitochondrion is the major source of reactive oxygen species. Hence, protecting mitochondria from oxidative damage can be an effective therapeutic strategy for the prevention of hypertensive heart disease. Conventional antioxidants are not likely to be cardioprotective, as they cannot protect mitochondria from oxidative damage. EUK-134 is a salen-manganese complex with superoxide dismutase and catalase activity. The possible role of EUK-134, a mitoprotective antioxidant, in the prevention of hypertrophy of H9C2 cells was examined. The cells were stimulated with phenylephrine (50 μM), and hypertrophy was assessed based on cell volume and expression of brain natriuretic peptide and calcineurin. Enhanced myocardial lipid peroxidation and protein carbonyl content, accompanied by nuclear factor-kappa B gene expression, confirmed the presence of oxidative stress in hypertrophic cells. Metabolic shift was evident from reduction in the expression of medium-chain acyl-CoA dehydrogenase. Mitochondrial oxidative stress was confirmed by the reduced expression of mitochondria-specific antioxidant peroxiredoxin-3 and enhanced mitochondrial superoxide production. Compromised mitochondrial function was apparent from reduced mitochondrial membrane potential. Pretreatment with EUK-134 (10 μM) was effective in the prevention of hypertrophic changes in H9C2 cells, reduction of oxidative stress, and prevention of metabolic shift. EUK-134 treatment improved the oxidative status of mitochondria and reversed hypertrophy-induced reduction of mitochondrial membrane potential. Supplementation with EUK-134 is therefore identified as a novel approach to attenuate cardiac hypertrophy and lends scope for the development of EUK-134 as a therapeutic agent in the management of human cardiovascular disease.
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    Mitoprotective antioxidant EUK-134 stimulates fatty acid oxidation and prevents hypertrophy in H9C2 cells
    (MOLECULAR AND CELLULAR BIOCHEMISTRY, 2016) Purushothaman, S; Nair, RR
    Oxidative stress is an important contributory factor for the development of cardiovascular diseases like hypertension-induced hypertrophy. Mitochondrion is the major source of reactive oxygen species. Hence, protecting mitochondria from oxidative damage can be an effective therapeutic strategy for the prevention of hypertensive heart disease. Conventional antioxidants are not likely to be cardioprotective, as they cannot protect mitochondria from oxidative damage. EUK-134 is a salen-manganese complex with superoxide dismutase and catalase activity. The possible role of EUK-134, a mitoprotective antioxidant, in the prevention of hypertrophy of H9C2 cells was examined. The cells were stimulated with phenylephrine (50 mu M), and hypertrophy was assessed based on cell volume and expression of brain natriuretic peptide and calcineurin. Enhanced myocardial lipid peroxidation and protein carbonyl content, accompanied by nuclear factor-kappa B gene expression, confirmed the presence of oxidative stress in hypertrophic cells. Metabolic shift was evident from reduction in the expression of medium-chain acyl-CoA dehydrogenase. Mitochondrial oxidative stress was confirmed by the reduced expression of mitochondria-specific antioxidant peroxiredoxin-3 and enhanced mitochondrial superoxide production. Compromised mitochondrial function was apparent from reduced mitochondrial membrane potential. Pretreatment with EUK-134 (10 mu M) was effective in the prevention of hypertrophic changes in H9C2 cells, reduction of oxidative stress, and prevention of metabolic shift. EUK-134 treatment improved the oxidative status of mitochondria and reversed hypertrophy-induced reduction of mitochondrial membrane potential. Supplementation with EUK-134 is therefore identified as a novel approach to attenuate cardiac hypertrophy and lends scope for the development of EUK-134 as a therapeutic agent in the management of human cardiovascular disease.
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    Negative inotropic response to cerium in ventricular papillary muscle is mediated by reactive oxygen species
    (BIOLOGICAL TRACE ELEMENT RESEARCH, 2003)
    This study was performed with the objective of assessing the mechanical response of the myocardium. to different levels of cerium and delineation of the mechanism underlying the mediation of the functional changes. Rat ventricular papillary muscle was used as the experimental model. Isolated papillary muscles were exposed to different concentrations of CeCl3 and the force of contraction was measured using a force transducer. Experiments have revealed that the negative inotropic response to CeCl3 was proportional to its concentration. The inotropic changes were found to be completely reversible at concentrations less than or equal to 5 muW, and partially reversible at higher concentrations. Neutralization of cerium-induced inotropic changes by the superoxide anion scavenger superoxide dismutase (SOD) at concentrations less than or equal to 5 muW indicates that the mechanical changes are mediated by reactive oxygen species. At higher concentrations of Ce3+, SOD partially reversed the contractile changes. The beneficial effect of SOD was seen only if the muscles were pretreated with the scavenger prior to the addition of cerium chloride.
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    Orchidectomy Reduced Abdominal Aorta Relaxation Response to Androgens in Sprague-Dawley Rats Fed a High Salt Diet
    (FASEB JOURNAL, 2011) Oloyo, AK; Sofola, OA; Anigbogu, CN; Nair, RR; Harikrishnan, V
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    Outcome of pregnancy among women with epilepsy in Kerala, India.
    (EPILEPSIA, 1999) Thomas, SV; Radhakrishnan, K; Devi, G; Jacob, S; Nair, RR; Kesavadas, K; Sarma, PS; Indrani, L; Beegam, J; Jacob, P
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    Reduction of perifusate magnesium alters inotropic response of papillary muscle to ion channel modulators
    (MAGNESIUM RESEARCH, 2005)
    Magnesium has a significant role in the regulation of ion transport. Marginal deficiency of Mg can therefore affect myocardial excitability and contractility. This study was taken up with the objective of examining the inotropic response of the, myocardium to variation in extracellular [Mg]. and identifying the ion channels and pumps mediating the inotropic changes. Electrically stimulated rat papillary muscle was used as the experimental model and mechanical changes were recorded using a physiograph. Channel specific antagonists were used to identify the channels mediating the functional. changes. Diastolic Ca2+ levels were determined in isolated myocytes by the ratiometric method using the fluorescent indicator Fura2-AM. A negative association was observed between the level of [Mg](O) and force of contraction, with a peak at 0.48 mM Mg. The force of contraction in Mg deficient medium (0.48 mM) was 158% of control (1.2 mM Mg) (p < 0.001). lnotropic response to the L-type channel antagonist (verapamil-1 mu m) and NaK ATPase inhibitor (Ouabain-0.3 mM) was augmented in Mg deficiency (p < 0.005), indicating activation of the channel and the pump. The response to T-type channel inhibitor (NiCl2-40 mu M) was attenuated in Mg deficiency (p < 0.05). The response to the sarcoplasmic reticular Ca pump inhibitor (caffeine-10 mM) and the SR Ca2+ release channel inhibitor (ryanodine-1 mu M) were not significantly affected by Mg deficiency. Diastolic level of Ca2+ increased with a decrease in Mg (p < 0.05). The observations of the study lead to the conclusion that the positive inotropic response in Mg deficiency is mediated by an increase in basal Ca2+ combined with Ca-induced-Ca release consequent to Ca2+ influx through L-type Ca channel. Variation insensitivity to Ca channel blockers and NaK ATPase inhibitor in Mg deficiency can have pharmacological implications.
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    Stimulation of cardiac fibroblast proliferation by cerium: a superoxide anion-mediated response
    (JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1999)
    Cardiac fibroblasts play a multifarious role in the maintenance of the functional and structural integrity of the heart. Therefore inadvertent proliferation of these fibroblasts can affect the normal functioning of the heart. The proliferation of fibroblasts could be due to various factors. We have worked on the hypothesis that low levels of cerium may stimulate cardiac fibroblasts to undergo proliferation and that free radicals act as the mediators of the stimulatory response. Cardiac fibroblasts isolated from neonatal Wistar rats were cultured. Proliferation of the cells was measured by cell count and immunohistochemical visualization for proliferating cell nuclear antigen, The response to cerium was assessed by comparison with control. A stimulatory response at low levels of cerium was observed with a peak at 0.5 mu M concentration of cerium. A concomitant increase in the generation of free radicals was also seen. The cerium-stimulated cell proliferation and free radical generation was neutralized by the inclusion of superoxide dismutase in the culture medium.Conclusion: Low doses of cerium, at levels comparable to those found in the serum of patients with EMF, has a stimulatory effect on cardiac fibroblasts and the abrogation of proliferation by antioxidant superoxide dismutase indicates that superoxide anion acts as a biological intermediate in cerium-induced cardiac fibroblast proliferation. (C) 1999 Academic Press.
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    Superoxide anions mediate proliferative response in cardiac fibroblasts
    (INDIAN JOURNAL OF MEDICAL RESEARCH, 2000) Preeta, R; Nair, RR
    The study was undertaken to examine whether superoxide anions mediate a proliferative response in cardiac fibroblasts. Cardiac fibroblasts isolated from newborn Wistar rats were exposed to superoxide anion generating system (hypoxanthine + xanthine oxidase) and its effect on cell growth was assessed. A stimulatory response on fibroblast proliferation was observed. The proportion of proliferating cells increased within 3 h of treatment compared to the control and the cell density after 96 h of exposure remained significantly high (P<0.0005). Inclusion of antioxidants neutralised the stimulatory response, fortifying the role of superoxide anions in cell proliferation. This observation indicates that superoxide anions can mediate a fibrotic reaction in the cardiac tissue.
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    Targeting Histamine-2 receptor for prevention of cardiac remodelling in chronic pressure overload
    (International Journal of Cardiology, 2016-01) Potnuri, AG; Allakonda, L; Appavoo, A; Saheera, S; Nair, RR
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    TNF-alpha depresses endocardial endothelial cell mediated proliferation of cardiac fibroblasts
    (JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2005) Kuruvilla, L; Nair, RR; Lal, AV; Umashankar, PR; Kartha, CC
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    Variation in mitogenic response of cardiac and pulmonary fibroblasts to cerium
    (BIOLOGICAL TRACE ELEMENT RESEARCH, 2003)
    Fibroproliferative response of rat heart and lung fibroblasts to the lanthanide cerium was examined, as the element has been implicated in the causation of cardiac and pulmonary fibrosis. Fibroblasts from both of the organs were morphologically identical, and the response to fetal bovine serum, a nonspecific mitogen, was also comparable. The oxygen radical generator (hypoxanthine + xanthine oxidase [Hyp. + XO]) induced a proliferative response that was neutralized in both cardiac and lung fibroblasts by free-radical scavengers. Superoxide dismutase was more effective than catalase in reducing the mitogenic effect of Hyp. + XO. The free-radical scavenger N-acetyl-L-cysteine neutralized the free-radical-mediated changes in pulmonary fibroblasts but had a negative effect in cardiac fibroblasts, indicating a tissue-dependent variation. Reactive oxygen species are known to act as biological mediators of tissue fibrosis induced by metallic compounds. Exposure to low levels of cerium (0.5 muM) stimulated a mitogenic response in cardiac fibroblasts, but the pulmonary fibroblasts were not sensitized by the element. Tissue-dependent variation in proliferative response to cerium shows a positive association with intracellular generation of reactive oxygen species. Fibrotic changes in cerium pneumoconiosis may either be replacement fibrosis following tissue damage or mediated by nonfibroblastic cells. The study confirms that cardiac and pulmonary fibroblasts are dissimilar cellular subtypes.