Detection of soluble BAG3 and anti-BAG3 antibodies in patients with chronic heart failure

Marco, Margot De; Falco, Antonia; Basile, Anna; Rosati, Alessandra; Festa, Michela; d’Avenia, Morena; Pascale, Maria; Piaz, Fabrizio Dal; Bisogni, Rita; Barcaroli, Daniela; Coppola, Giangennaro; Piscione, Federico; Gigantino, Alberto; Citro, Rodolfo; Rosa, Roberta De; Vitulano, Gennaro; Virtuoso, Nicola; Manganelli, Fiore; Palermo, Ester; Siano, Francesco; Rosato, Giuseppe; Hahne, Michael; Tiberti, Claudio; Laurenzi, Vincenzo De; Turco, Maria Caterina

doi:10.1038/cddis.2013.8

Cited by 29 publications

(33 citation statements)

References 8 publications

(9 reference statements)

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“…13 Our studies performed in a cohort of patients with chronic HF have revealed increased levels of BAG3 in the serum of patients affected by a more advanced stage of HF, suggesting that BAG3 protein may represent a useful biomarker in monitoring HF progression. 14, 24 In addition, other reports have proposed elevated serum levels of BAG3 as a novel prognostic marker in patients with acutely decompensated HF (ADHF).…”

Section: Discussionmentioning

confidence: 72%

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The prosurvival protein BAG3: a new participant in vascular homeostasis

et al. 2016

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Bcl2-associated athanogene 3 (BAG3), is constitutively expressed in a few normal cell types, including myocytes, peripheral nerves and in the brain, and is also expressed in certain tumors. To date, the main studies about the role of BAG3 are focused on its pro-survival effect in tumors through various mechanisms that vary according to cellular type. Recently, elevated concentrations of a soluble form of BAG3 were described in patients affected by advanced stage of heart failure (HF), identifying BAG3 as a potentially useful biomarker in monitoring HF progression. Despite the finding of high levels of BAG3 in the sera of HF patients, there are no data on its possible role on the modulation of vascular tone and blood pressure levels. The aim of this study was to investigate the possible hemodynamic effects of BAG3 performing both in vitro and in vivo experiments. Through vascular reactivity studies, we demonstrate that BAG3 is capable of evoking dose-dependent vasorelaxation. Of note, BAG3 exerts its vasorelaxant effect on resistance vessels, typically involved in the blood pressure regulation. Our data further show that the molecular mechanism through which BAG3 exerts this effect is the activation of the PI3K/Akt signalling pathway leading to nitric oxide release by endothelial cells. Finally, we show that in vivo BAG3 administration is capable of regulating blood pressure and that this is dependent on eNOS regulation since this ability is lost in eNOS KO animals.

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Section: Discussionmentioning

confidence: 72%

“…13 Further study revealed serum BAG3 protein values were increased in patients affected by a more advanced stage of heart failure (HF), suggesting BAG3 protein might be a potentially useful biomarker in monitoring HF progression. 14 Finally, we demonstrated that BAG3 was prognostic in patients presenting with acutely decompensated HF (ADHF).…”

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confidence: 99%

The prosurvival protein BAG3: a new participant in vascular homeostasis

et al. 2016

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“…the expression of BaG3 can be induced by a variety of stimuli such as the early growth response gene-1 (egr-1) (28), heat shock factor 1 (HSf1) (29), proteasome inhibitors (30), heavy metals as well as heat stress (31,32). Previous studies indicated that BaG3 is involved in various cVd such as myocardial hypertrophy, dilated cardiomyopathy, takotsubo cardiomyopathy and chronic heart failure (10)(11)(12)(13). in the present study, we first confirmed that the expression of BAG3 increased with continued passages in cultured primary rat VSmcs.…”

Section: Discussionmentioning

confidence: 99%

“…Bcl-2-associated athanogene 3 (BaG3) is a member of BaG family and plays an important role in diverse cellular behaviors including cell apoptosis, autophagy, proliferation, adhesion, migration and differentiation (6)(7)(8)(9). accumulating evidence indicates that BaG3 is associated with various cardiovascular diseases such as myocardial hypertrophy, dilated cardiomyopathy, takotsubo cardiomyopathy and chronic heart failure (10)(11)(12)(13). normal tissues seldom express BaG3, except for cardiomyocytes and skeletal muscle cells, but its expression is induced upon exposure to various stressful stimuli (14).…”

Section: Introductionmentioning

confidence: 99%

BAG3 promotes the phenotypic transformation of primary rat vascular smooth muscle cells via TRAIL

Chen

et al. 2018

Int J Mol Med

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Under normal physiological condition, the mature vascular smooth muscle cells (VSMCs) show differentiated phenotype. In response to various environmental stimuluses, VSMCs convert from the differentiated phenotype to dedifferentiated phenotype characterized by the increased ability of proliferation/migration and the reduction of contractile ability. The phenotypic transformation of VSMCs played an important role in atherosclerosis. Both Bcl-2-associated athanogene 3 (BAG3) and tumor necrosis factor-related apopt-osis inducing ligand (TRAIL) involved in apoptosis. The relationship between BAG3 and TRAIL and their effects the proliferation and migration in VSMCs are rarely reported. This study investigated the effects of BAG3 on the phenotypic modulation and the potential underlying mechanisms in primary rat VSMCs. Primary rat VSMCs were extracted and cultured in vitro. Cell proliferation was detected by cell counting, real-time cell analyzer (RTCA) and EdU incorporation. Cell migration was detected by wound healing, Transwell and RTCA. BAG3 and TRAIL were detected using real-time PCR and western blotting and the secreted proteins in the cultured media by dot blot. The expression of BAG3 increased with continued passages in cultured primary VSMCs. BAG3 promoted the proliferation and migration of primary rat VSMC in a time-dependent manner. BAG3 significantly increased the expression of TRAIL while had no effects on its receptors. TRAIL knockdown or blocking by neutralizing antibody inhibited the proliferation of VSMCs induced by BAG3. TRAIL knockdown exerted no obvious influence on the migration of VSMCs. Based on this study, we report for the first time that BAG3 was expressed in cultured primary rat VSMCs and the expression of BAG3 increased with continued passages. Furthermore, BAG3 promoted the proliferation of VSMCs via increasing the expression of TRAIL. In addition, we also demonstrated that BAG3 promoted the migration of VSMCs independent of TRAIL upregulation.

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“…Under physiological conditions, BAG3 protein expression appears to be restricted to few cell types including skeletal muscle cells and cardiomyocytes [Hishiya et al, ; De Marco et al, , ]. Its expression; however, can be induced in different normal cell types (leukocytes, epithelial, glial, and retinal cells) by a variety of stressors, such as oxidants, high temperature, serum deprivation, and it is thought to contribute to resistance to metabolic stress [Pagliuca et al, ; Rosati et al, , ; Ammirante et al, ].…”

Section: Discussionmentioning

confidence: 99%

Whole exome sequencing identified 1 base pair novel deletion in BCL2‐associated athanogene 3 (BAG3) gene associated with severe dilated cardiomyopathy (DCM) requiring heart transplant in multiple family members

Rafiq

Chaudhry

Care

et al. 2017

American J of Med Genetics Pt A

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Dilated cardiomyopathy (DCM) is characterized by dilation and impaired contraction of the left ventricle or both ventricles. Among hereditary DCM, the genetic causes are heterogeneous, and include mutations encoding cytoskeletal, nucleoskeletal, mitochondrial, and calcium-handling proteins. We report three severely affected males, in a four-generation pedigree, with DCM phenotype who underwent cardiac transplant. Cardiomegaly with marked biventricular dilation and fibrosis were noticeable histopathological findings. The affected males had tested negative on a 46-gene pancardiomyopathy panel. Whole Exome Sequencing (WES) was performed to reveal mutation in the gene responsible in generation of DCM phenotypes. The 1-bp (Chr10:121435979delC; c.913delC) novel heterozygous deletion in exon 4 of BAG3, was identified in three affected males, resulted in frame-shift and a premature termination codon (p.Met306-Stop) producing a truncated BAG3 protein lacking functionally important PXXP and BAG domains. WES data were further utilized to map 10 SNP markers around the discovered mutation to generate shared disease haplotype in all affected individuals encompassing 11 Mb on 10q25.3-26.2 harboring BAG3. Finally genotypes were inferred for the unavailable/deceased individuals in the pedigrees. Here we propose that Chr10:121435979delC in BAG3 is a causal mutation in these subjects. Our and earlier studies indicate that BAG3 mutations are associated with DCM phenotypes. BAG3 should be added to cardiomyopathy gene panels for screening of DCM patients, and patients previously considered gene elusive should undergo sequencing of the BAG3 gene. © 2017 Wiley Periodicals, Inc.

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Detection of soluble BAG3 and anti-BAG3 antibodies in patients with chronic heart failure

Cited by 29 publications

References 8 publications

The prosurvival protein BAG3: a new participant in vascular homeostasis

The prosurvival protein BAG3: a new participant in vascular homeostasis

BAG3 promotes the phenotypic transformation of primary rat vascular smooth muscle cells via TRAIL

Whole exome sequencing identified 1 base pair novel deletion in BCL2‐associated athanogene 3 (BAG3) gene associated with severe dilated cardiomyopathy (DCM) requiring heart transplant in multiple family members

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