C M Caldarera

Universita degli studi di Ferrara, Ferrare, Emilia-Romagna, Italy

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Publications (184)

  • [Show abstract] [Hide abstract] ABSTRACT: Introduction Cardiovascular diseases are a major cause of mortality in industrialized countries. Patients who survive after an acute myocardial infarction (AMI) are prone to ventricular remodeling, resulting from loss of myocardial tissue, and to progressive chronic heart failure (CHF). Heart has just a minimal potential of repair and regeneration, thus the use of new strategies of treatment involving stem cell transplantation and/or endogenous stem cell mobilization is expected to be a promising alternative to standard therapy. Stem cells are undifferentiated cells with self-renewal and differentiation potential. Among stem cells, embryonic (ESCs) are considered as the best for cardiac regeneration (Nir et al., 2003); on the other hand several issues, including ethical questions, immunorejection, and teratoma formation, limit their practical use. To overcome these restrictions, research interest is focusing on adult stem cells, identified in different tissues and found to be able to differentiate towards the cardiac phenotype. Stem cells obtained from bone marrow contain a subpopulation of hematopoietic stem cells (HSCs) (Goodell et al., 1997), a component of mesenchymal stem cells (MSCs) (Pittenger and Martin, 2004), and multipotent progenitor cells (MAPCs) (Jiang et al., 2002). MSCs derived from bone marrow show some potential of differentiation into beating cardiomyocytes in vitro (Makino et al., 1999; Fukuda, 2001; Hakuno et al., 2002; Toma et al., 2002). Somatic stem cells also include endothelial progenitor cells (EPCs), obtained from peripheral circulation (Badorff et al., 2003), and cells derived from umbilical cord (USSCs). USSCs showed capacity of differentiation towards the cardiac phenotype and to promote angiogenesis (Badorff et al., 2003; Kogler et al., 2004). Resident stem cells, located in cardiac niches, showed a differentiation potential towards cardiomyocytes (Bollini et al., 2010). In the last decade another group of somatic stem cells, derived from adipose tissue (ADSCs), has been studied, most of all for their easy mode of extraction, relative abundance, and differentiative capacity towards different lineages.
    Article · Jan 2012
  • [Show abstract] [Hide abstract] ABSTRACT: Recent studies have shown that aldosterone may play a critical role in the transition to heart failure and that heart is a direct target of the action of aldosterone, which can provoke hypertrophy and apoptosis of isolated cardiomyocytes and also increase the expression of genes that favor tissue fibrosis. Early work from this and other laboratories has established a link between the aliphatic polyamines and cardiac hypertrophy, while more recently an involvement of polyamines even in cell death and survival has emerged. In the present study we have treated cardiac cells, i.e. rat H9c2 cardiomyoblasts and neonatal cardiomyocytes, with (D, L)-2-(difluoromethyl)ornithine, a specific inhibitor of polyamine biosynthesis, to investigate the effects of polyamines in relation to the hypertrophic, pro-fibrotic and pro-apoptotic actions of aldosterone. The results indicate that inhibition of polyamine biosynthesis may prevent or attenuate the adverse actions of aldosterone, by modulating the expression of genes related to cardiac hypertrophy and fibrosis, as well as the levels of proteins and the activities of enzymes that control apoptosis.
    Article · Dec 2009 · Amino Acids
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    [Show abstract] [Hide abstract] ABSTRACT: The fabrication of biodegradable 3-D scaffolds enriched with multipotent stem cells seems to be a promising strategy for the repair of irreversibly injured tissues. The fine mechanisms of the interaction of rat mesenchymal stem cells (rMSCs) with a hyaluronan-based scaffold, i.e. HYAFF(R)11, were investigated to evaluate the potential clinical application of this kind of engineered construct. rMSCs were seeded (2 x 10(6) cells cm(-2)) on the scaffold, cultured up to 21 days and analysed using appropriate techniques. Light (LM), scanning (SEM) and transmission (TEM) electron microscopy of untreated scaffold samples showed that scaffolds have a highly porous structure and are composed of 15-microm-thick microfibres having a rough surface. As detected by trypan blue stain, cell adhesion was high at day 1. rMSCs were viable up to 14 days as shown by CFDA assay and proliferated steadily on the scaffold as revealed by MTT assay. LM showed rMSCs in the innermost portions of the scaffold at day 3. SEM revealed a subconfluent cell monolayer covering 40 +/- 10% of the scaffold surface at day 21. TEM of early culture showed rMSCs wrapping individual fibres with regularly spaced focal contacts, whereas confocal microscopy showed polarized expression of CD44 hyaluronan receptor; TEM of 14-day cultures evidenced fibronexus formation. Immunohistochemistry of 21-day cultures showed that fibronectin was the main matrix protein secreted in the extracellular space; decorin and versican were seen in the cell cytoplasm only and type IV collagen was minimally expressed. The expression of CD90, a marker of mesenchymal stemness, was found unaffected at the end of cell culture. Our results show that HYAFF(R)11 scaffolds support the adhesion, migration and proliferation of rMSCs, as well as the synthesis and delivery of extracellular matrix components under static culture conditions without any chemical induction. The high retention rate and viability of the seeded cells as well as their fine modality of interaction with the substrate suggest that such scaffolds could be potentially useful when wide tissue defects are to be repaired as in the case of cartilage repair, wound healing and large vessel replacement.
    Full-text Article · Dec 2008 · Journal of Anatomy
  • Article · Apr 2008 · Journal of Molecular and Cellular Cardiology
  • F Flamigni · I Stanic · A Facchini · [...] · C M Caldarera
    [Show abstract] [Hide abstract] ABSTRACT: Growing evidence suggests a role for polyamines in apoptosis, although the relationship appears to be complex. alpha-Difluoromethylornithine (DFMO), a largely used ornithine decarboxylase inhibitor, is cytostatic, hardly cytotoxic and may even increase the resistance of tumour cells to some apoptotic stimuli. This may represent a problem in cancer therapy, where the killing of tumoral cells would be a desired effect, but could be an advantage in other pathological contexts related to an excess of apoptosis, such as cardiovascular diseases, stem cell transplantation, arthritis and infections. In different cellular models, polyamine depletion following treatment with polyamine biosynthesis inhibitors appears to inhibit mitochondrial and death receptor pathways of apoptosis by affecting key proteins. These studies indicate that inhibition of polyamine biosynthesis may prevent or reduce the apoptotic response triggered by a variety of stimuli in non-tumoral cells, such as cardiac cells, stem cells, chondrocytes, macrophages and intestinal epithelial cells.
    Article · Sep 2007 · Amino Acids
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    [Show abstract] [Hide abstract] ABSTRACT: Recent developments in the field of protein separation allows for the analysis of qualitative and quantitative global protein changes in a particular state of a biological system. Due to the enormous number of proteins potentially present in a cell, sub-fractionation and the enrichment of specific organelles are emerging as a necessary step to allow a more comprehensive representation of the protein content. The proteomic studies demonstrate that a key to understand the mechanisms underlying physiological or pathological phenotypes lies, at least in part, in post-translational modifications (PTMs), including phosphorylation of proteins. Rapid improvements in proteomic characterization of amino acid modifications are further expanding our comprehension of the importance of these mechanisms. The present review will provide an overview of technologies available for the study of a proteome, including tools to assess changes in protein quantity (abundance) as well as in quality (PTM forms). Examples of the recent application of these technologies and strategies in the field of kinase signalling will be provided with particular attention on the role of PKC in the heart. Studies of PKC-mediated phosphorylation of cytoskeletal, myofilament and mitochondrial proteins in the heart have provided great insight into the phenotypes of heart failure, hypertrophy and cardioprotection. Proteomics studies of the mitochondria have provided novel evidences for kinase signalling cascades localized to the mitochondria, some of which are known to involve various isoforms of PKC. Proteomics technologies allow for the identification of the different PTM forms of specific proteins and this information is likely to provide insight into the determinants of morphological as well as metabolic mal-adaptations, both in the heart and other tissues.
    Full-text Article · Jul 2007 · Pharmacological Research
  • Article · Jun 2007 · Journal of Molecular and Cellular Cardiology
  • Article · Jun 2007 · Journal of Molecular and Cellular Cardiology
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    Full-text Article · Mar 2007 · Journal of Molecular and Cellular Cardiology
  • Article · Sep 2006 · Journal of Molecular and Cellular Cardiology
  • Article · Jun 2006 · Journal of Molecular and Cellular Cardiology
  • [Show abstract] [Hide abstract] ABSTRACT: Several studies show that inflammatory components may contribute to atherosclerosis and increase the risk for myocardial infarction (MI). Interleukin-6 (IL-6) is a key pro-inflammatory and immune-modulatory cytokine of relevance for cardiovascular diseases. In this case-control study, 200 patients with MI and 257 healthy controls were genotyped for the polymorphism present in -174 promoter region of the IL-6 gene. Plasma concentrations of IL-6 and C-reactive protein (CRP) in a group of patients and controls were measured. The -174 C allele was associated with an increased risk of developing MI (OR = 2.886, c.i. = 1.801-4.624, P = 0.0001) in older patients, while no association was found in younger ones. The IL-6 plasma levels were higher in patients with MI carrying the CC genotype than in GG patients (CC carriers, IL-6 = 2.97 pg mL(-1) vs. GG carriers = 1.81 pg mL(-1), P = 0.016). A positive correlation of IL-6 levels with those of CRP in serum from patients with MI was also found. Data from this study suggest that the C allele of the promoter polymorphism in the IL-6 gene is a risk factor for MI in the elderly, and the production of the IL-6 is differentially affected by different genotypes of the IL-6 -174 promoter polymorphism.
    Article · Jan 2006 · International Journal of Immunogenetics
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    [Show abstract] [Hide abstract] ABSTRACT: Hypoxia/reoxygenation (H/R) is one of the causes of the increased expression of inducible nitric oxide synthase (iNOS) in cardiomyocytes. Since an aberrant NOS induction has detrimental consequences, we evaluated the effect of a green tea extract (GTE) on the NOS induction and activity in H/R-cardiomyocytes to define a nutritional strategy. Cultured rat cardiomyocytes were exposed to H/R in the presence of two concentrations of a green tea extract (GTE), which is reported to inhibit NOS expression and activity in different cells. In cultured cardiomyocytes two NOS isoforms were constitutively expressed, but only iNOS was induced by H/R. GTE supplementation at the lowest concentration, comparable to that in human plasma after dietary consumption, was ineffective, while the highest, comparable to that achievable by dietary supplements, counteracted the effect of H/R on iNOS induction and activity. It is necessary to verify in humans the relationship between the modulation of NO production and green tea dietary consumption.
    Full-text Article · Jun 2005 · Biochimie
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    D Lio · G Candore · A Crivello · [...] · C Caruso
    Full-text Article · Nov 2004 · Journal of Medical Genetics
  • [Show abstract] [Hide abstract] ABSTRACT: In a previous research, we have shown that adequate levels of polyamines are required in transformed mouse fibroblasts for the correlated activations of MAPK subtypes (ERK and JNK) and caspases induced by etoposide and leading to apoptosis. We report now that the treatment of fibroblasts with etoposide also elicited a progressive and sustained increase of NF-kappaB activation. The DNA binding activity of p65 NF-kappaB subunit was increased up to approximately 4-fold and was accompanied by enhancement of p65 phosphorylation. A two days pre-treatment of fibroblasts with alpha-difluoromethylornithine (DFMO), which caused polyamine depletion, provoked a slight activating effect when given alone, but markedly inhibited the etoposide-induced increases in p65 DNA binding and phosphorylation. The NF-kappaB inhibiting effect of DFMO was prevented by the addition of exogenous putrescine, which restored the intracellular content of polyamines. Selective inhibitors of the etoposide-stimulated MAPK subtypes also reduced NF-kappaB activation. Moreover, pharmacological NF-kappaB inhibition reduced the increase in caspase activity and cell death elicited by etoposide, suggesting that NF-kappaB is involved in signaling to apoptosis. The results of the present study, together with our previous findings, suggest that polyamines play a permissive role in the pathways triggered by etoposide and leading to cell death of fibroblasts, by supporting the activation of MAPKs, NF-kappaB and caspases.
    Article · Nov 2004 · Amino Acids
    Article · Jun 2003 · European Journal of Heart Failure Supplements
  • F. Bonafè · C. Muscari · C. Guarnieri · C.M. Caldarera
    [Show abstract] [Hide abstract] ABSTRACT: The ventricular remodeling following an acute myocardial infarction generates a non-contractile fibrous scare which might provoke cardiac failure. Several techniques aimed at recovering myocardial performance through the utilization of stem cells have been investigated in these last years. Embryonal stem cells, although they are characterized by an elevated differentiation potential, present technical and ethical concerns. Thus, most studies have been addressed towards adult (somatic) stem cells. Three categories of adult stem cells are now mainly investigated: a) satellite cells from skeletal muscle, b) mesenchymal stem cells from bone marrow, c) stem cells which are eventually present in the cardiac tissue. Skeletal myoblasts, even if they are not able to differentiate in cardiomyocytes, can improve cardiac contractility at the level of the fibrous scare which substitutes the necrotic area. It is also possible to isolate stem cells from bone marrow which can originate several cell lines, among them cardiac muscle cells and endothelial cells. Finally, more recent studies have demonstrated that resident cardiomyocytes maintain the capability to duplicate: therefore, a population of myocardial progenitors might be able to replicate and repair the damaged tissue. A deeper investigation of these findings in the clinical field could lead to the identification of new therapeutic strategies aimed at ameliorating the cardiac performance of the infarcted patients for short and long periods.
    Article · Jan 2003
  • Conference Paper · Jan 2002
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    B Tantini · F Flamigni · C Pignatti · [...] · C M Caldarera
    [Show abstract] [Hide abstract] ABSTRACT: We have recently shown that tumor necrosis factor-alpha (TNFalpha) and lipopolysaccharide (LPS) stimulate DNA synthesis in chick embryo cardiomyocytes (CMs). The aim of the present research was to investigate the pathways involved in this mitogenic response. CMs were isolated from 10-day-old chick embryos and grown to confluence. After 20 h of serum starvation the cells were treated with TNFalpha and LPS, and/or specific agonists and antagonists to manipulate the levels of polyamines, NO, cGMP and their biosynthetic enzymes ornithine decarboxylase (ODC), nitric oxide synthase (NOS) and soluble guanylate cyclase (sGC). ODC, NOS, sGC activities and cGMP contents were determined by radiochemical procedures. DNA synthesis was determined by incorporation of [3H]-thymidine. Treatment of CMs with TNFalpha and LPS increased cell number and [3H]-thymidine incorporation. Addition of TNFalpha and LPS provoked an induction of ODC, with consequent polyamine accumulation, and a more delayed enhancement of NOS activity, which appeared to be independent of the activation of the ODC-polyamine system. TNFalpha and LPS treatment also enhanced cGMP level in CMs and both polyamine and NO biosyntheses appeared to be required. Experiments with specific inhibitors of ODC and NOS, as well as with inhibitors of sGC and cGMP-dependent protein kinase (PKG), showed that polyamine-, NO- and cGMP-dependent pathways are required for the mitogenic action of TNFalpha and LPS. Moreover, addition of exogenous polyamines to untreated cells raised the cGMP level in a NO-dependent fashion, and enhanced [3H]-thymidine incorporation. The latter effect was inhibited by sGC or PKG inhibitors. Treatment of quiescent cells with NO donors, 8-bromo-cGMP or YC-1, an sGC activator, also promoted DNA synthesis. Furthermore, putrescine and NO donor can additively activate sGC in cell-free extracts. TNFalpha and LPS stimulate DNA synthesis in chick embryo CMs and this effect is mediated by polyamines, NO and intracellular cGMP.
    Full-text Article · Mar 2001 · Cardiovascular Research
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    Full-text Article · Jun 2000 · European Journal of Heart Failure

Publication Stats

2k Citations


  • 2008
    • Universita degli studi di Ferrara
      • Section of Cardiology
      Ferrare, Emilia-Romagna, Italy
  • 1977-2003
    • University of Bologna
      • • Department of Biomedical Science and Neuromotor Sciences DIBINEM
      • • School of Medicine
      Bolonia, Emilia-Romagna, Italy