Inhibition of vascular calcification by block of intermediate conductance calcium-activated potassium channels with TRAM-34

Freise, Christian; Querfeld, Uwe

doi:10.1016/j.phrs.2014.04.013

Cited by 29 publications

(29 citation statements)

References 49 publications

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“…Intracellular calcium influx resulting from depolarization-induced VGCC opening has been associated with SMC differentiation (58). However, a long-term increase in intracellular calcium is linked to osteogenic differentiation of SMCs, and inhibition of intracellular calcium intake by K Ca blocker attenuates calcium phosphate-induced VSMC calcification (59). In addition, inhibition of L-type calcium channels by verapamil has been shown to reduce VSMC calcification (60).…”

Section: Discussionmentioning

confidence: 99%

Dietary potassium regulates vascular calcification and arterial stiffness

Sun¹,

Byon²,

Yang³

et al. 2017

JCI Insight

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Section: Discussionmentioning

confidence: 99%

Dietary potassium regulates vascular calcification and arterial stiffness

Sun¹,

Byon²,

Yang³

et al. 2017

JCI Insight

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“…The matrix metalloproteinases (MMPs) are a group of Zn-dependent endopeptidases which controls ECM synthesis and degradation, including collagen and elastin [10; 11; 12; 13; 14]. An alteration of MMP activity over prolonged period of time causes adverse ECM remodeling which is often seen in fibrotic diseases such as diabetic nephropathy [8; 15].…”

Section: Introductionmentioning

confidence: 99%

MMP-9- and NMDA receptor-mediated mechanism of diabetic renovascular remodeling and kidney dysfunction: Hydrogen sulfide is a key modulator

2015

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Previously we reported that matrix metalloproteinase-9 (MMP-9) plays an important role in extracellular matrix (ECM) remodeling in diabetic kidney. Induction of NMDA-R and dysregulation of connexins (Cxs) were also observed. We concluded that this was due to decreased H2S production by down regulation of CBS and CSE enzymes. However, the potential role of H2S to mitigate ECM dysregulation and renal dysfunction was not clearly understood. The present study was undertaken to determine whether H2S supplementation reduces MMP-9-induced ECM remodeling and dysfunction in diabetic kidney. Wild type (C57BL/6J), diabetic (Akita, C57BL/6J-Ins2Akita), MMP-9 knockout (MMP-9−/− , M9KO) and double KO of Akita/MMP-9−/− (DKO) mice were treated without or with 0.05 g/L of NaHS (as a source of H2S) in drinking water for 30 days. Decreased tissue production and plasma content of H2S in Akita mice were ameliorated with H2S supplementation. Dysregulated expression of MMP-9, CBS, CSE, NMDA-R1 and Cxs-40, -43 were also normalized in Akita mice treated with H2S. In addition, increased renovascular resistive index (RI), ECM deposition, plasma creatinine, and diminished renal vascular density and cortical blood flow in Akita mice were normalized with H2S treatment. We conclude that diminished H2S production in renal tissue and plasma levels in diabetes mediates adverse renal remodeling, and H2S therapy improves renal function through MMP-9- and NMDA-R1-mediated pathway.

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“…To investigate this issue, we used an established in vitro model of vascular calcification which enables the induction of calcification/transdifferentiation of VSMC with elevated concentrations of calcium and phosphorus (Ca/P) [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

ALindera obtusilobaExtract Blocks Calcium-/Phosphate-Induced Transdifferentiation and Calcification of Vascular Smooth Muscle Cells and Interferes with Matrix Metalloproteinase-2 and Metalloproteinase-9 and NF-κB

Freise

Kim

Querfeld

2015

Evidence-Based Complementary and Alternative Medicine

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Vascular calcifications bear the risk for cardiovascular complications and have a high prevalence among patients with chronic kidney disease. Central mediators of vascular calcifications are vascular smooth muscle cells (VSMC). They transdifferentiate into a synthetic/osteoblast-like phenotype, which is induced, for example, by elevated levels of calcium and phosphate (Ca/P) due to a disturbed mineral balance. An aqueous extract from Lindera obtusiloba (LOE) is known to exert antifibrotic and antitumor effects or to interfere with the differentiation of preadipocytes. Using murine and rat VSMC cell lines, we here investigated whether LOE also protects VSMC from Ca/P-induced calcification. Indeed, LOE effectively blocked Ca/P-induced calcification of VSMC as shown by decreased VSMC mineralization and secretion of alkaline phosphatase. In parallel, mRNA expression of the calcification markers osterix and osteocalcin was reduced. Vice versa, the Ca/P-induced loss of the VSMC differentiation markers alpha smooth muscle actin and smooth muscle protein 22-alpha was rescued by LOE. Further, LOE blocked Ca/P-induced mRNA expressions and secretions of matrix metalloproteinases-2/-9 and activation of NF-κB, which are known contributors to vascular calcification. In conclusion, LOE interferes with the Ca/P-induced transdifferentiation/calcification of VSMC. Thus, LOE should be further analysed regarding a potential complementary treatment option for cardiovascular diseases including vascular calcifications.

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Inhibition of vascular calcification by block of intermediate conductance calcium-activated potassium channels with TRAM-34

Cited by 29 publications

References 49 publications

Dietary potassium regulates vascular calcification and arterial stiffness

Dietary potassium regulates vascular calcification and arterial stiffness

MMP-9- and NMDA receptor-mediated mechanism of diabetic renovascular remodeling and kidney dysfunction: Hydrogen sulfide is a key modulator

ALindera obtusilobaExtract Blocks Calcium-/Phosphate-Induced Transdifferentiation and Calcification of Vascular Smooth Muscle Cells and Interferes with Matrix Metalloproteinase-2 and Metalloproteinase-9 and NF-κB

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