Novel Identification of Ankyrin-R in Cardiac Fibroblasts and a Potential Role in Heart Failure.
Aaron D ArgallHolly C Sucharski-ArgallLuke G ComisfordSallie J JursJack T SeminettaMichael J WallaceCasey A CrawfordSarah S TakenakaMei HanMona El RefaeyThomas J HundPeter J MohlerSara N KoenigPublished in: International journal of molecular sciences (2024)
Altered ankyrin-R (AnkR; encoded by ANK1 ) expression is associated with diastolic function, left ventricular remodeling, and heart failure with preserved ejection fraction (HFpEF). First identified in erythrocytes, the role of AnkR in other tissues, particularly the heart, is less studied. Here, we identified the expression of both canonical and small isoforms of AnkR in the mouse myocardium. We demonstrate that cardiac myocytes primarily express small AnkR (sAnkR), whereas cardiac fibroblasts predominantly express canonical AnkR. As canonical AnkR expression in cardiac fibroblasts is unstudied, we focused on expression and localization in these cells. AnkR is expressed in both the perinuclear and cytoplasmic regions of fibroblasts with considerable overlap with the trans-Golgi network protein 38, TGN38, suggesting a potential role in trafficking. To study the role of AnkR in fibroblasts, we generated mice lacking AnkR in activated fibroblasts ( Ank1 -ifKO mice). Notably, Ank1 -ifKO mice fibroblasts displayed reduced collagen compaction, supportive of a novel role of AnkR in normal fibroblast function. At the whole animal level, in response to a heart failure model, Ank1 -ifKO mice displayed an increase in fibrosis and T-wave inversion compared with littermate controls, while preserving cardiac ejection fraction. Collagen type I fibers were decreased in the Ank1 -ifKO mice, suggesting a novel function of AnkR in the maturation of collagen fibers. In summary, our findings illustrate the novel expression of AnkR in cardiac fibroblasts and a potential role in cardiac function in response to stress.
Keyphrases
- left ventricular
- heart failure
- poor prognosis
- extracellular matrix
- ejection fraction
- aortic stenosis
- high fat diet induced
- cardiac resynchronization therapy
- binding protein
- hypertrophic cardiomyopathy
- mitral valve
- magnetic resonance imaging
- blood pressure
- long non coding rna
- gene expression
- wild type
- wound healing
- oxidative stress
- stress induced
- pi k akt
- heat stress