Bradykinin Type-2 Receptor Expression Correlates with Age and Is Subjected to Transcriptional Regulation
Accumulating work in experimental animals suggests that bradykinin (BK) exerts cardioprotective effects via bradykinin type-2 receptors (BK-2Rs). In human end-stage heart failure, BK-2Rs are significantly downregulated by mechanisms that have remained elusive. Heart tissues from idiopathic dilated c...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | International Journal of Vascular Medicine |
| Online Access: | http://dx.doi.org/10.1155/2012/159646 |
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| author | Inka Liesmaa Naotaka Shiota Jorma O. Kokkonen Petri T. Kovanen Ken A. Lindstedt |
| author_facet | Inka Liesmaa Naotaka Shiota Jorma O. Kokkonen Petri T. Kovanen Ken A. Lindstedt |
| author_sort | Inka Liesmaa |
| collection | DOAJ |
| description | Accumulating work in experimental animals suggests that bradykinin (BK) exerts cardioprotective effects via bradykinin type-2 receptors (BK-2Rs). In human end-stage heart failure, BK-2Rs are significantly downregulated by mechanisms that have remained elusive. Heart tissues from idiopathic dilated cardiomyopathy (IDC; 𝑛=7), coronary heart disease (CHD; 𝑛=6), and normal patients (𝑛=6) were analyzed by RT-PCR, SSCP, and Western blotting. In normal and IDC hearts, BK-2R expression increased with age, with a lower relative increase in IDC hearts. BK-2R mRNA and protein levels showed a positive linear correlation, suggesting transcriptional regulation. Two known BK-2R promoter polymorphisms, −58T/C and −9/+9, were found to be present in the study population. The allelic frequencies for the C-allele in −58T/C were 0.58 in normal and CHD hearts and 0.81 in IDC hearts. Furthermore, the allelic frequencies for the −9 and +9 alleles were 0.42 and 0.58 in normal hearts and 0.64 and 0.36 in IDC hearts, respectively. All analyzed CHD hearts were homozygous for the −9 allele. Thus, the expression of cardioprotective BK-2Rs in human hearts is increased with age in normal and IDC hearts and may be regulated on the transcriptional level. Moreover, comparison of normal subjects and patients with failing hearts revealed different allelic frequencies in each of two known BK-2R gene polymorphisms. |
| format | Article |
| id | doaj-art-f24ee2634aac45dd9efb4172b014f3e2 |
| institution | Kabale University |
| issn | 2090-2824 2090-2832 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Vascular Medicine |
| spelling | doaj-art-f24ee2634aac45dd9efb4172b014f3e22025-02-03T01:26:23ZengWileyInternational Journal of Vascular Medicine2090-28242090-28322012-01-01201210.1155/2012/159646159646Bradykinin Type-2 Receptor Expression Correlates with Age and Is Subjected to Transcriptional RegulationInka Liesmaa0Naotaka Shiota1Jorma O. Kokkonen2Petri T. Kovanen3Ken A. Lindstedt4Wihuri Research Institute, Kalliolinnantie 4, 00140 Helsinki, FinlandWihuri Research Institute, Kalliolinnantie 4, 00140 Helsinki, FinlandWihuri Research Institute, Kalliolinnantie 4, 00140 Helsinki, FinlandWihuri Research Institute, Kalliolinnantie 4, 00140 Helsinki, FinlandWihuri Research Institute, Kalliolinnantie 4, 00140 Helsinki, FinlandAccumulating work in experimental animals suggests that bradykinin (BK) exerts cardioprotective effects via bradykinin type-2 receptors (BK-2Rs). In human end-stage heart failure, BK-2Rs are significantly downregulated by mechanisms that have remained elusive. Heart tissues from idiopathic dilated cardiomyopathy (IDC; 𝑛=7), coronary heart disease (CHD; 𝑛=6), and normal patients (𝑛=6) were analyzed by RT-PCR, SSCP, and Western blotting. In normal and IDC hearts, BK-2R expression increased with age, with a lower relative increase in IDC hearts. BK-2R mRNA and protein levels showed a positive linear correlation, suggesting transcriptional regulation. Two known BK-2R promoter polymorphisms, −58T/C and −9/+9, were found to be present in the study population. The allelic frequencies for the C-allele in −58T/C were 0.58 in normal and CHD hearts and 0.81 in IDC hearts. Furthermore, the allelic frequencies for the −9 and +9 alleles were 0.42 and 0.58 in normal hearts and 0.64 and 0.36 in IDC hearts, respectively. All analyzed CHD hearts were homozygous for the −9 allele. Thus, the expression of cardioprotective BK-2Rs in human hearts is increased with age in normal and IDC hearts and may be regulated on the transcriptional level. Moreover, comparison of normal subjects and patients with failing hearts revealed different allelic frequencies in each of two known BK-2R gene polymorphisms.http://dx.doi.org/10.1155/2012/159646 |
| spellingShingle | Inka Liesmaa Naotaka Shiota Jorma O. Kokkonen Petri T. Kovanen Ken A. Lindstedt Bradykinin Type-2 Receptor Expression Correlates with Age and Is Subjected to Transcriptional Regulation International Journal of Vascular Medicine |
| title | Bradykinin Type-2 Receptor Expression Correlates with Age and Is Subjected to Transcriptional Regulation |
| title_full | Bradykinin Type-2 Receptor Expression Correlates with Age and Is Subjected to Transcriptional Regulation |
| title_fullStr | Bradykinin Type-2 Receptor Expression Correlates with Age and Is Subjected to Transcriptional Regulation |
| title_full_unstemmed | Bradykinin Type-2 Receptor Expression Correlates with Age and Is Subjected to Transcriptional Regulation |
| title_short | Bradykinin Type-2 Receptor Expression Correlates with Age and Is Subjected to Transcriptional Regulation |
| title_sort | bradykinin type 2 receptor expression correlates with age and is subjected to transcriptional regulation |
| url | http://dx.doi.org/10.1155/2012/159646 |
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