Verapamil inhibits ureteral scar formation by regulating CaMK II-mediated Smad pathway

Zeng, Mingqiang; Xiao, Wei; Yang, Ke; Gao, Zhiyong; Wang, Jiansong; Lü, Qiang; Guo, Xi; Li, Yuanwei; Wu, Yuan

doi:10.1016/j.cbi.2021.109570

Cited by 11 publications

(8 citation statements)

References 22 publications

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“…We also report for the first time, a significant increase in immature collagen fibers present in the tunica media of the ascending aortas of CD animals. In accordance with previous studies implicating verapamil with collagen synthesis (Zeng et al, 2021), and the role of curcumin in better maturation and cross linking of collagen (Panchatcharam et al, 2006), after CURVER treatment the increase in immature fibers observed in untreated CD mice was significantly reduced. This process could contribute to the remodeling of the ascending aorta, reducing the thickness of the tunica media and augmenting the lumen diameter.…”

Section: Discussionsupporting

confidence: 92%

Curcumin combined with verapamil improve cardiovascular phenotype of a Williams-Beuren Syndrome mice model reducing oxidative stress

Abdalla

Ortiz‐Romero

Rodriguez-Rovira

et al. 2022

Preprint

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Williams-Beuren syndrome (WBS) is a rare neurodevelopmental disorder with hallmarks in the cardiovascular manifestations and no well-defined therapeutic strategies. We investigated the progression of cardiovascular phenotype present in CD (complete deletion) mice, a murine model of WBS, after chronic treatment with curcumin and verapamil, both compounds with positive effects on related pathologies. Treatment was administered orally dissolved in drinking water. After measuring in-vivo systolic blood pressure, aortic and left ventricular myocardium were histological and molecular analysed to determine the effects of treatment and its underlying mechanism in CD mice. We observed upregulated xanthine oxidoreductase (XOR) expression in both aortic and left ventricular myocardium of CD mice. This overexpression is concomitant with increased levels of nitrated proteins as example of byproduct-mediated oxidative stress damage, indicating of XOR-generated oxidative stress impact on the pathophysiology of cardiovascular manifestations in WBS, and suggesting that the inhibition of XOR and/or oxidative stress damage could help to ameliorate the severe cardiovascular injuries presented in WBS.

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Section: Discussionsupporting

confidence: 92%

Curcumin combined with verapamil improve cardiovascular phenotype of a Williams-Beuren Syndrome mice model reducing oxidative stress

Abdalla

Ortiz‐Romero

Rodriguez-Rovira

et al. 2022

Preprint

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“…We showed similar findings in dcSSc fibroblasts in this study in the context of the BET or BRD4 inhibitors. In addition to cardiac fibrosis, CaMKII is also involved in pulmonary fibrosis (32), ureteral scar formation (33), and renal fibrosis (34). CaMKII is associated with FGFR3/FGF9 in SSc fibroblasts, functioning as a downstream mediator of the profibrotic effect of FGFR3 (25).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of bromodomain extraterminal histone readers alleviates skin fibrosis in experimental models of scleroderma

Vichaikul¹,

Gurrea-Rubio²,

Amin³

et al. 2022

JCI Insight

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“…Undoubtedly, blocking of VDCC has led to decreased free Ca 2+ and in turn decreased CAMKII. VRP can also inhibit transforming growth factor beta 1 (TGF-β1), which was found to trigger CAMKII (Zeng et al 2021 ). Our results are in agreement with previous studies reported that VRP can downregulate CAMKII (Zeng et al 2021 ; Gao et al 2021 ; Mooney et al 2015 ).…”

Section: Discussionmentioning

confidence: 99%

“…VRP can also inhibit transforming growth factor beta 1 (TGF-β1), which was found to trigger CAMKII (Zeng et al 2021 ). Our results are in agreement with previous studies reported that VRP can downregulate CAMKII (Zeng et al 2021 ; Gao et al 2021 ; Mooney et al 2015 ). Fortunately, suppression of CAMKII together with the restored mitochondria and anti-inflammatory effect decreased the level of pTAU.…”

Section: Discussionmentioning

confidence: 99%

Chronotherapeutic neuroprotective effect of verapamil against lipopolysaccharide-induced neuroinflammation in mice through modulation of calcium-dependent genes

Mosalam

Elberri

Sallam

et al. 2022

Mol Med

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Background Neuroinflammation is a major mechanism in neurodegenerative diseases such as Alzheimer’s disease (AD), which is a major healthcare problem. Notwithstanding of ample researches figured out possible molecular mechanisms underlying the pathophysiology of AD, there is no definitive therapeutics that aid in neuroprotection. Therefore, searching for new agents and potential targets is a critical demand. We aimed to investigate the neuroprotective effect of verapamil (VRP) against lipopolysaccharide (LPS)-induced neuroinflammation in mice and whether the time of VRP administration could affect its efficacy. Methods Forty male albino mice were used and were divided into normal control, LPS only, morning VRP, and evening VRP. Y-maze and pole climbing test were performed as behavioral tests. Hematoxylin and eosin together with Bielschowsky silver staining were done to visualize neuroinflammation and phosphorylated tau protein (pTAU); respectively. Additionally, the state of mitochondria, the levels of microglia-activation markers, inflammatory cytokines, intracellular Ca2+, pTAU, and Ca2+-dependent genes involving Ca2+/ calmodulin dependent kinase II (CAMKII) isoforms, protein kinase A (PKA), cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF), with the level of VRP in the brain tissue were measured. Results LPS successfully induced neuroinflammation and hyperphosphorylation of tau protein, which was indicated by elevated levels of microglia markers, inflammatory cytokines, and intracellular Ca2+ with compromised mitochondria and downregulated CAMKII isoforms, PKA, CREB and BDNF. Pretreatment with VRP showed significant enhancement in the architecture of the brain and in the behavioral tests as indicated by the measured parameters. Moreover, morning VRP exhibited better neuroprotective profile compared to the evening therapy. Conclusions VRP highlighted a multilevel of neuroprotection through anti-inflammatory activity, Ca2+ blockage, and regulation of Ca2+-dependent genes. Furthermore, chronotherapy of VRP administration should be consider to achieve best therapeutic efficacy. Graphical Abstract

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Verapamil inhibits ureteral scar formation by regulating CaMK II-mediated Smad pathway

Cited by 11 publications

References 22 publications

Curcumin combined with verapamil improve cardiovascular phenotype of a Williams-Beuren Syndrome mice model reducing oxidative stress

Curcumin combined with verapamil improve cardiovascular phenotype of a Williams-Beuren Syndrome mice model reducing oxidative stress

Inhibition of bromodomain extraterminal histone readers alleviates skin fibrosis in experimental models of scleroderma

Chronotherapeutic neuroprotective effect of verapamil against lipopolysaccharide-induced neuroinflammation in mice through modulation of calcium-dependent genes

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