Citations to this article
Citation Information: JCI Insight. 2019;4(22):e131092. https://doi.org/10.1172/jci.insight.131092.
Abstract
Aging is a major risk factor for cardiovascular disease. Although the impact of aging has been extensively studied, little is known regarding the aging processes in cells of the heart. Here we analyzed the transcriptomes of hearts of 12-week-old and 18-month-old mice by single-nucleus RNA-sequencing. Among all cell types, aged fibroblasts showed most significant differential gene expression, increased RNA dynamics, and network entropy. Aged fibroblasts exhibited significantly changed expression patterns of inflammatory, extracellular matrix organization angiogenesis, and osteogenic genes. Functional analyses indicated deterioration of paracrine signatures between fibroblasts and endothelial cells in old hearts. Aged heart-derived fibroblasts had impaired endothelial cell angiogenesis and autophagy and augmented proinflammatory response. In particular, expression of Serpine1 and Serpine2 were significantly increased and secreted by old fibroblasts to exert antiangiogenic effects on endothelial cells, an effect that could be significantly prevented by using neutralizing antibodies. Moreover, we found an enlarged subpopulation of aged fibroblasts expressing osteoblast genes in the epicardial layer associated with increased calcification. Taken together this study provides system-wide insights and identifies molecular changes of aging cardiac fibroblasts, which may contribute to declined heart function.
Authors
Ramon Vidal, Julian Uwe Gabriel Wagner, Caroline Braeuning, Cornelius Fischer, Ralph Patrick, Lukas Tombor, Marion Muhly-Reinholz, David John, Magdalena Kliem, Thomas Conrad, Nuno Guimarães-Camboa, Richard Harvey, Stefanie Dimmeler, Sascha Sauer
Citations to this article in year 2023 (24)
| Title and authors | Publication | Year |
|---|---|---|
|
Spatiotemporal changes of tissue glycans depending on localization in cardiac aging
Itakura Y, Hasegawa Y, Kikkawa Y, Murakami Y, Sugiura K, Nagai-Okatani C, Sasaki N, Umemura M, Takahashi Y, Kimura T, Kuno A, Ishiwata T, Toyoda M |
Regenerative Therapy | 2023 |
|
Diabetes and Its Cardiovascular Complications: Potential Role of the Acetyltransferase p300
Di Pietrantonio N, Di Tomo P, Mandatori D, Formoso G, Pandolfi A |
Cells | 2023 |
|
Fibroblast heterogeneity: Keystone of tissue homeostasis and pathology in inflammation and ageing
Gauthier V, Kyriazi M, Nefla M, Pucino V, Raza K, Buckley CD, Alsaleh G |
Frontiers in immunology | 2023 |
|
Deciphering endothelial heterogeneity in health and disease at single-cell resolution: progress and perspectives.
Becker LM, Chen SH, Rodor J, de Rooij LPMH, Baker AH, Carmeliet P |
Cardiovascular Research | 2023 |
|
Fibroblast and Immune Cell Cross-Talk in Cardiac Fibrosis.
Hara A, Tallquist MD |
Current Cardiology Reports | 2023 |
|
Analysis of cardiac single-cell RNA-sequencing data can be improved by the use of artificial-intelligence-based tools.
Nguyen T, Wei Y, Nakada Y, Chen JY, Zhou Y, Walcott G, Zhang J |
Scientific Reports | 2023 |
|
Single-cell and spatial transcriptomics: Advances in heart development and disease applications.
Long X, Yuan X, Du J |
Computational and Structural Biotechnology Journal | 2023 |
|
Single-cell transcriptomic analysis uncovers diverse and dynamic senescent cell populations
Wechter N, Rossi M, Anerillas C, Tsitsipatis D, Piao Y, Fan J, Martindale JL, De S, Mazan-Mamczarz K, Gorospe M |
Aging | 2023 |
|
Understanding tumour endothelial cell heterogeneity and function from single-cell omics.
Zeng Q, Mousa M, Nadukkandy AS, Franssens L, Alnaqbi H, Alshamsi FY, Safar HA, Carmeliet P |
Nature reviews. Cancer | 2023 |
|
A Multimodal Omics Framework to Empower Target Discovery for Cardiovascular Regeneration.
Li Z, Brittan M, Mills NL |
Cardiovascular Drugs and Therapy | 2023 |
|
Identification of autophagy-associated circRNAs in sepsis-induced cardiomyopathy of mice
Zheng MZ, Lou JS, Fan YP, Fu CY, Mao XJ, Li X, Zhong K, Lu LH, Wang LL, Chen YY, Zheng LR |
Scientific Reports | 2023 |
|
Extracellular Vesicles and Cardiac Aging.
Seara FAC, Maciel L, Kasai-Brunswick TH, Nascimento JHM, Campos-de-Carvalho AC |
Advances in experimental medicine and biology | 2023 |
|
The role of immunosuppressive myofibroblasts in the aging process and age-related diseases.
Salminen A |
Journal of Molecular Medicine | 2023 |
|
Cardiac fibroblast GSK-3α aggravates ischemic cardiac injury by promoting fibrosis, inflammation, and impairing angiogenesis.
Umbarkar P, Ejantkar S, Ruiz Ramirez SY, Toro Cora A, Zhang Q, Tousif S, Lal H |
Basic Research in Cardiology | 2023 |
|
Fibulin-3 is necessary to prevent cardiac rupture following myocardial infarction
Murtha LA, Hardy SA, Mabotuwana NS, Bigland MJ, Bailey T, Raguram K, Liu S, Ngo DT, Sverdlov AL, Tomin T, Birner-Gruenberger R, Hume RD, Iismaa SE, Humphreys DT, Patrick R, Chong JJ, Lee RJ, Harvey RP, Graham RM, Rainer PP, Boyle AJ |
Scientific Reports | 2023 |
|
A 4D transcriptomic map for the evolution of multiple sclerosis-like lesions in the marmoset brain
Lin JP, Brake A, Donadieu M, Lee A, Kawaguchi R, Sati P, Geschwind DH, Jacobson S, Schafer DP, Reich DS |
2023 | |
|
An interferon gamma response signature links myocardial aging and immunosenescence
Ashour D, Rebs S, Arampatzi P, Saliba AE, Dudek J, Schulz R, Hofmann U, Frantz S, Cochain C, Streckfuß-Bömeke K, Campos Ramos G |
Cardiovascular Research | 2023 |
|
The rate of epigenetic drift scales with maximum lifespan across mammals
Bertucci-Richter EM, Parrott BB |
Nature Communications | 2023 |
|
AMPK signaling inhibits the differentiation of myofibroblasts: impact on age-related tissue fibrosis and degeneration.
Salminen A |
Biogerontology | 2023 |
|
Endothelial cell dysfunction: the culprit for cardiac denervation in aging?
Moore OM, Keefe JA, Wehrens XH |
2023 | |
|
Fibroblast Reprogramming in Cardiac Repair
Wang Q, Spurlock B, Liu J, Qian L |
JACC: Basic to Translational Science | 2023 |
|
Identification and functional analysis of senescent cells in the cardiovascular system using omics approaches
Mahoney SA, Dey AK, Basisty N, Herman AB |
American journal of physiology. Heart and circulatory physiology | 2023 |
|
ACTIVATED FIBROBLASTS IN CANCER: PERSPECTIVES AND CHALLENGES
Caligiuri G, Tuveson DA |
Cancer Cell | 2023 |
|
Recent advances and future prospects in direct cardiac reprogramming.
Xie Y, Van Handel B, Qian L, Ardehali R |
Nature cardiovascular research | 2023 |
