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| Status |
Public on Aug 09, 2023 |
| Title |
PCSK9, a promising novel target for age-related cardiovascular dysfunction |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Cardiovascular diseases (CVD) are the leading cause of death among elderly people. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important regulator of cholesterol metabolism. Herein, we investigated the role of PCSK9 in age-related CVD. Both in humans and rats, sPCSK9 correlated positively with increasing age and the development of cardiovascular dysfunction. Network analysis identified PCSK9 as an important factor in age-associated lipid alterations and it correlated positively with intima media thickness, a clinical parameter of CVD risk. PCSK9 inhibition with alirocumab effectively reduced the CVD progression in aging rats suggesting that PCSK9 plays an important role in cardiovascular aging.
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| Overall design |
A population-based screening program and the iNetModels database were used to explore the PCSK9’s role in cardiovascular aging in humans. A rat model of advanced aging was applied to study age-related cardiovascular/hepatic changes and to investigate the effects of PCSK9 inhibition on cardiovascular aging.
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| Contributor(s) |
Matyas C, Trojnar E, Zhao S, Arif M, Mukhopadhyay P, Kovacs A, Fabian A, Tokodi M, Bagyura Z, Merkely B, Kohidai L, Lajko E, Takacs A, He Y, Gao B, Paloczi J, Lohoff F, Hasko G, Ding W, Pacher P |
| Citation(s) |
38094682 |
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| Submission date |
Feb 22, 2023 |
| Last update date |
Jan 02, 2024 |
| Contact name |
Muhammad Arif |
| E-mail(s) |
muhammad.arif@nih.gov
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| Organization name |
National Institutes of Health
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| Department |
National Institute of Alcohol Abuse and Alcoholism
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| Street address |
5625 Fishers Lane
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| City |
Rockville |
| State/province |
Maryland |
| ZIP/Postal code |
20852 |
| Country |
USA |
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| Platforms (1) |
| GPL25947 |
Illumina NovaSeq 6000 (Rattus norvegicus) |
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| Samples (12)
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| GSM7058765 |
Heart, Y5, Young |
| GSM7058766 |
Heart, Y6, Young |
| GSM7058767 |
Heart, Y7, Young |
| GSM7058773 |
Heart, A1, Aging |
| GSM7058774 |
Heart, A2, Aging |
| GSM7058775 |
Heart, A4, Aging |
| GSM7058776 |
Heart, A5, Aging |
| GSM7058777 |
Heart, A6, Aging |
| GSM7058778 |
Heart, A10, Aging |
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| Relations |
| BioProject |
PRJNA937728 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE225859_RAW.tar |
2.3 Mb |
(http)(custom) |
TAR (of TXT) |
| GSE225859_fpkm_genename.txt.gz |
2.3 Mb |
(ftp)(http) |
TXT |
| GSE225859_readcount_genename.txt.gz |
1.5 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
| Processed data provided as supplementary file |
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