Diltiazem, a calcium antagonist, inhibits matrix metalloproteinase-1 (tissue collagenase) production and collagenolytic activity in human vascular smooth muscle cells

Wada, Yasuhiko; Kato, Seiya; Okamoto, Kenichi; Izumaru, Shinsuke; Aoyagi, Shigeaki; Morimatsu, Minoru

doi:10.3892/ijmm.8.5.561

Cited by 10 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…3A). In the BrdU incorporation assay, cells were cultured in DMEM supplemented with or without 10 ng/ml of PDGF for 24 h and then subsequently incubated with BrdU-labeling solution for an additional 4 h. We previously reported observing maximal Sphasic entry 24 h after PDGF stimulation of quiescent SMC (38). Consistently with the data of cell counting, BrdU incorporation assay showed a significant reduction of PDGFinduced RASMC proliferation when ß2-chimaerin was expressed by adenoviral means (Fig.…”

Section: Expression Of Endogenous ß2-chimaerin In Human Smc and Exogesupporting

confidence: 82%

Regulation of vascular smooth muscle proliferation and migration by β2-chimaerin, a non-protein kinase C phorbol ester receptor

Maeda

Kato²,

Fukushima³

et al. 2006

Int J Mol Med

Self Cite

View full text Add to dashboard Cite

The proliferation and migration of vascular smooth muscle cells (SMC) are important aspects of atherogenesis. Activated growth factor signaling in injured vessels subsequently promotes a number of intracellular events resulting in the phenotypic modulation of SMC. Here, we investigated the role of ß2-chimaerin, a non-protein kinase C phorbol ester receptor with Rac-GTPase-activating protein activity, in growth factor-stimulated SMC. The endogenous expression of ß2chimaerin was detected in cultured human SMC by reverse transcription-polymerase chain reaction and immunohistochemistry. Next, the overexpression of HA-tagged wild-type human ß2-chimaerin was attempted using cultured rat SMC with a recombinant adenovirus (Adv-ß2-Chim). Adv-LZ encoding ß-galactosidase (LacZ) was used as the control. The proliferation of SMC stimulated by platelet-derived growth factor (PDGF-BB, 10 ng/ml), as measured by cell-counting and 5-bromo-2'deoxyuridine incorporation assay, was suppressed by infection with Adv-ß2-Chim (50-200 MOI), but not with control viruses. PDGF-induced SMC migration was inhibited by approximately 25% after infection with Adv-ß2-Chim (200 MOI) using a modified Boyden's chamber assay with a fibronectin-coated membrane. Confocal microscopy revealed that PDGF stimulation altered the sub-cellular localization of ß2-chimaerin. The administration of 12-O-tetradecanoyl phorbol 13-acetate also induced changes in the sub-cellular localization of ß2-chimaerin, which was not affected by a presence of the PKC inhibitor (GF109203X). Finally, PDGFinduced Rac1 activation was found to be inhibited in the Adv-ß2-Chim-infected cells. Thus, we demonstrated that ß2chimaerin regulates the proliferation and migration of SMC downstream of growth factor signaling pathway via the regulation of Rac1 activity. The signaling mediated by ß2chimaerin may play a role in the regulation of SMC phenotypes, thereby implicating human atherogenesis.

show abstract

Section: Expression Of Endogenous ß2-chimaerin In Human Smc and Exogesupporting

confidence: 82%

Regulation of vascular smooth muscle proliferation and migration by β2-chimaerin, a non-protein kinase C phorbol ester receptor

Maeda

Kato²,

Fukushima³

et al. 2006

Int J Mol Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, this finding has been disputed in some published work (Campistol et al, 2001). On the other hand, calcium channel blockers have also been reported to modulate the activity/expression of MMPs and TIMPs, but the mechanisms of action are still unclear (Roth et al, 1996;Wada et al, 2001). Cholesterol-lowering drugs, the statins, can reduce tissue fibrosis (Louneva et al, 2006) by their ability to inhibit angiotensin-induced connective tissue growth factor production (CTGF) (Rupérez et al, 2007).…”

Section: B Other Current Drugs With Beneficial Diseasemodifying Propmentioning

confidence: 99%

“…Blocking of the L-type calcium channel (Mason et al, 2003) Inhibition of collagen expression and accumulation (Roth et al, 1996;Sugiura et al, 2000); modulation of MMP activity (Roth et al, 1996;Wada et al, 2001) Calcium sensitizing drugs e.g., Levosimendan…”

Section: Antimicrobial Drugmentioning

confidence: 99%

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

et al. 2009

View full text Add to dashboard Cite

“…106 -108 Recently, various CCBs, including amlodipine, have been reported to modulate MMP activity. 109,110 Although the mechanisms of action involved are still unclear, CCBs might act not only on MMP activity/expression but also on transcription of the tissue inhibitor of metalloproteinases (TIMPs). 107,109 It has also been reported that several CCBs, including amlodipine, prevented induction of the hydroxymethyl glutaryl coenzyme A reductase gene and enhanced platelet-derived growth factor-BB induced LDL receptor gene and expression.…”

Section: Other Effectsmentioning

confidence: 99%

Novel Vascular Biology of Third-Generation L-Type Calcium Channel Antagonists

Mason

Marché

Hintze

2003

ATVB

156

117

View full text Add to dashboard Cite

Abstract-Calcium channel blockers (CCBs) were developed as vasodilators, and their use in cardiovascular disease treatment remains largely based on that mechanism of action. More recently, with the evolution of second-and third-generation CCBs, pleiotropic effects have been observed, and at least some of CCBs' benefit is attributable to these mechanisms. Understanding these effects has contributed greatly to elucidating disease mechanisms and the rationale for CCB use. Furthermore, this knowledge might clarify why drugs are useful in some disease states, such as atherosclerosis, but not in others, such as heart failure. Although numerous drugs used in the treatment of vascular disease, including statins and angiotensin-converting-enzyme inhibitors, have well-described pleiotropic effects universally accepted to contribute to their benefit, little attention has been paid to CCBs' potentially similar effects.Accumulating evidence that at least 1 CCB, amlodipine, has pharmacologic actions distinct from L-type calcium channel blockade prompted us to investigate the pleiotropic actions of amlodipine and CCBs in general. There are several areas of research; foci here are (1) the physicochemical properties of amlodipine and its interaction with cholesterol and oxidants; (2) the mechanism by which amlodipine regulates NO production and implications; and (3) amlodipine's role in controlling smooth muscle cell proliferation and matrix formation.

show abstract

Diltiazem, a calcium antagonist, inhibits matrix metalloproteinase-1 (tissue collagenase) production and collagenolytic activity in human vascular smooth muscle cells

Cited by 10 publications

References 0 publications

Regulation of vascular smooth muscle proliferation and migration by β2-chimaerin, a non-protein kinase C phorbol ester receptor

Regulation of vascular smooth muscle proliferation and migration by β2-chimaerin, a non-protein kinase C phorbol ester receptor

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

Novel Vascular Biology of Third-Generation L-Type Calcium Channel Antagonists

Contact Info

Product

Resources

About