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Expression of Ca(2+) Transport Genes in Platelets and Endothelial Cells in Hypertension
Irina Mountian1, Fawzia Baba-Aïssa, Jean-Christophe Jonas
1Laboratorium voor Fysiologie (I.M., H.De S., F.W., J.B.P.), KU Leuven, Leuven, Belgium.
Insights
Hypertension alters calcium handling proteins, sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) and IP3R, in rat cells. ACE inhibitors normalized these changes, suggesting improved endothelial and platelet function.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Pharmacology
Background:
- Essential hypertension is linked to altered intracellular calcium (Ca2+) handling.
- Specific Ca2+ regulatory proteins, sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) and inositol 1,4,5-trisphosphate receptor (IP3R), are implicated.
Purpose of the Study:
- To investigate SERCA and IP3R isoform expression in platelets and aortic endothelial cells (EC) of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats.
- To determine the effects of ACE inhibitors (lisinopril and captopril) on these protein expressions.
Main Methods:
- Quantitative analysis using ratio reverse-transcriptase-polymerase chain reaction (RT-PCR) and Western blotting.
- Assessment of SERCA2b, SERCA3, IP3R1, IP3R2, and IP3R3 at mRNA and protein levels in isolated rat cells.
- Treatment of rats with lisinopril or captopril.
Main Results:
- SHR exhibited distinct expression patterns of SERCA3, IP3R1, and IP3R2 compared to WKY rats.
- ACE inhibitor treatment normalized SERCA and IP3R expression patterns in SHR to resemble WKY rats, except for SERCA mRNA in platelets.
- SERCA3 remained the predominant isoform, and IP3R2 was highly expressed in both EC and platelets post-treatment.
Conclusions:
- Altered SERCA and IP3R expression in SHR contributes to intracellular Ca2+ handling dysfunction.
- ACE inhibitors normalize these expression patterns, potentially improving endothelial and platelet function in hypertensive states.
- The normalized expression suggests a non-hypertensive cellular configuration induced by ACE inhibitors.
Abstract:
-Altered Ca(2+) handling is observed in different cells in essential hypertension. We investigated the expression of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) and inositol 1,4,5-trisphosphate receptor (IP(3)R) isoforms in platelets and aortic endothelial cells (EC) isolated from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats by ratio reverse-transcriptase-polymerase chain reaction (RT-PCR) analysis and Western blotting. SERCA2b and SERCA3 were assessed at mRNA (EC and platelets) and at protein level (platelets). IP(3)R1, IP(3)R2, and IP(3)R3 mRNAs were demonstrated in both cell types, but only IP(3)R1 and IP(3)R2 proteins were detected in platelets. Compared with WKY, SHR EC and platelets showed higher SERCA3 and IP(3)R2 expression and lower IP(3)R1 expression. We then investigated the effect of lisinopril (20 mg. kg(-)(1). d(-)(1); 10-week treatment of 4-week-old rats or 2-week treatment of adult rats) and captopril (100 mg. kg(-)(1). d(-)(1); 2-week treatment of adult rats). Consequently, expression patterns of SERCAs and IP(3)Rs were significantly modified. Except for SERCAs mRNA in platelets, all differences between SHR and WKY disappeared. However, SERCA3 remained the predominant isoform. Both EC and platelets demonstrated a high equal expression of IP(3)R2 mRNA. IP(3)R1 was the predominant platelet protein isoform, as it was in untreated WKY. mRNA was also isolated from pancreatic islets of WKY and SHR, but no effect of either rat strain or of lisinopril treatment was observed on the expression of the studied genes. We hypothesize that the identical expression pattern of SERCAs and IP(3)Rs after treatment with ACE inhibitors represents a different nonhypertensive configuration, which, through changes in intracellular Ca(2+) handling, improves endothelial and platelet dysfunction in SHR but has no effect in WKY.