Increased store-operated and 1-oleoyl-2-acetyl-sn-glycerol-induced calcium influx in monocytes is mediated by transient receptor potential canonical channels in human essential hypertension.

Abstract

OBJECTIVE:

Activation of nonselective cation channels of the transient receptor potential canonical (TRPC) family has been associated with hypertension. Whether store-operated channels, which are activated after depletion of intracellular stores, or second-messenger-operated channels, which are activated by 1-oleoyl-2-acetyl-sn-glycerol, are affected in essential hypertension is presently unknown.

METHODS:

Using a polymerase chain reaction, an in-cell western assay and the fluorescent dye technique we studied TRPC3, TRPC5, and TRPC6 expression and store-operated and 1-oleoyl-2-acetyl-sn-glycerol-induced calcium influx into human monocytes in 19 patients with essential hypertension and in 17 age-matched and sex-matched normotensive control individuals.

RESULTS:

We observed a significantly increased expression of TRPC3 and TRPC5, but not TRPC6, in essential hypertension. Store-operated calcium influx was significantly elevated in essential hypertension. Store-operated calcium influx was reduced by the inhibitor 2-aminoethoxydiphenylborane, specific TRPC3 and TRPC5 knockdown, but not TRPC6 knockdown using gene silencing by RNA interference. 1-Oleoyl-2-acetyl-sn-glycerol-induced calcium influx and barium influx were also significantly elevated in essential hypertension. The 1-oleoyl-2-acetyl-sn-glycerol-induced cation influx was reduced by TRPC3 and TRPC5 knockdown.

CONCLUSION:

We demonstrated an increased TRPC3 and TRPC5 expression and a subsequently increased store-operated calcium influx and increased 1-oleoyl-2-acetyl-sn-glycerol-induced cation influx in monocytes of patients with essential hypertension. This increased activation of monocytes through TRPC channels in patients with essential hypertension may promote vascular disease in these patients.

• Authors: Dao Yan Liu, Florian Thilo, Alexandra Scholze, Antje Wittstock, Zhi Gang Zhao, Christian Harteneck, Walter Zidek, Zhi Ming Zhu, Martin Tepel
• Journal: Journal of hypertension (J Hypertens) Vol. 25 Issue 4 Pg. 799-808 (Apr 2007) ISSN: 0263-6352 [Print] England
• PMID: 17351372 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channels
• Diglycerides
• RNA, Messenger
• TRPC Cation Channels
• TRPC3 cation channel
• TRPC5 protein, human
• TRPC6 Cation Channel
• TRPC6 protein, human
• 1-oleoyl-2-acetylglycerol
• Calcium

Topics

• Aged
• Blotting, Western
• Calcium (metabolism)
• Calcium Channels (metabolism)
• Case-Control Studies
• Diglycerides (administration & dosage, pharmacology)
• Dose-Response Relationship, Drug
• Down-Regulation (drug effects)
• Female
• Fluorescence
• Humans
• Hypertension (metabolism)
• Male
• Middle Aged
• Monocytes (drug effects, metabolism)
• RNA Interference
• RNA, Messenger (metabolism)
• Research Design
• Reverse Transcriptase Polymerase Chain Reaction
• TRPC Cation Channels (metabolism)
• TRPC6 Cation Channel