Key result
Ablating cardiac fibroblast primary cilia reduces collagen deposition and preserves EF post-MI in mice.
Why the study?
Post-MI cardiac fibrosis is a major contributor to heart failure without effective anti-fibrotic therapies, prompting investigation into whether genetic ablation of induced primary cilia on cardiac fibroblasts preserves cardiac function.
Does specific genetic ablation of primary cilia on cardiac fibroblasts improve cardiac function and reduce fibrosis in a mouse model of myocardial infarction?
Does specific genetic ablation of primary cilia on cardiac fibroblasts improve cardiac function and reduce fibrosis in a mouse model of myocardial infarction?
Genetic ablation of primary cilia on cardiac fibroblasts reduces fibrosis and preserves cardiac function post-myocardial infarction in mice, highlighting a potential novel therapeutic target for heart failure.
Answers are grounded in this paper and cite their sources.
Does not support clinical translation of fibroblast cilia targeting post-MI; hypothesis-generating for novel antifibrotic mechanisms in cardiac remodeling.
The progression of cardiac fibrosis following myocardial infarction (MI) is a major contributor to heart failure, yet effective anti-fibrotic therapies remain elusive. We have discovered a previously unappreciated regulatory mechanism: primary cilia, known as cellular antennae, are dramatically induced on cardiac fibroblasts (CFs) following injury. Notably, we observed a significant increase in ciliation incidence in CFs not only after acute MI (7 days post-Left anterior descending artery ligation, LAD ligation) but also in 1-year-old mdx mice (a model of chronic cardiomyopathy, Duchenne muscular dystrophy-associated cardiomyopathy), linking ciliary activation directly to both acute and chronic cardiac pathology. This discovery led us to hypothesize that these ciliary structures act as critical signaling hubs that drive the pro-fibrotic fate of CFs, and their specific genetic ablation would therefore preserve long-term heart function. To test this, we utilized a conditional genetic mouse model (PdgfrαCreERT x Ift88lox/lox), which specifically lacks primary cilia on CFs, and subjected these mice (n=9-12 per group per sex) to permanent LAD ligation to induce MI. Cardiac function (Ejection Fraction and Fractional Shortening) was serially assessed via echocardiography for three weeks, and fibrosis was quantified at 21 days post-MI using Sirius Red staining. Critically, the loss of primary cilia in CFs resulted in a significant reduction in collagen deposition in both the border (p< 0.01) and scar regions (p< 0.05) compared to control mice. Functionally, mice lacking CF cilia exhibited strikingly preserved Ejection Fraction and Fractional Shortening at 3 weeks post-MI (p< 0.05), confirming robust functional protection. Mechanistically, loss of cilia in both post-MI and mdx hearts correlates with reduced Hedgehog pathway activity and attenuated expression of pro-fibrotic genes. Analysis of a published single-cell RNA-sequencing dataset identifies Desert Hedgehog (DHH) as the predominant Hedgehog ligand induced post-LAD, linking injury-induced Hedgehog signaling to fibrotic gene programs that are blunted in the context of ciliary loss. Our findings not only define primary cilia on CFs as a novel regulator of cardiac remodeling but also reveal a new cellular pathway that can be explored for a targeted anti-fibrotic intervention. This work establishes ciliary signaling in CFs as a promising therapeutic target for preserving heart function and finally limiting the progression to heart failure after MI. This work was supported by the US National Institutes of Health (NIH) grants 1R01AR079449 to D.K. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
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Liu et al. (2026) studied Myocardial infarction and cardiac fibrosis. Genetic ablation of primary cilia on cardiac fibroblasts vs. Control mice was evaluated on Cardiac function (Ejection Fraction and Fractional Shortening) and fibrosis (collagen deposition) (p=<0.05). Genetic ablation of primary cilia on cardiac fibroblasts significantly reduced collagen deposition and preserved Ejection Fraction and Fractional Shortening at 3 weeks post-MI (p<0.05).
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