The interleukin-1 receptor type I promotes the development of aging-associated cardiomyopathy in mice

•Aging promotes diastolic dysfunction and fibrosis.•Genetic deletion of the IL-1RI protected mice from age-associated diastolic dysfunction.•IL-1RI deficiency mitigates interstitial myocardial fibrosis.•Interleukin-1 signaling promotes the development of aging-associated cardiomyopathy. Aging is ass...

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Published in:Cytokine (Philadelphia, Pa.) Pa.), 2022-03, Vol.151, p.155811-155811, Article 155811
Main Authors: Narayan, Pratyush, Trikantzopoulos, Elefterios, Mezzaroma, Eleonora, Mauro, Adolfo G., Vohra, Habeebah, Abbate, Antonio, Toldo, Stefano
Format: Article
Language:English
Subjects:
Age Factors
Aging
Animals
Cardiomyopathies - genetics
Cardiomyopathies - metabolism
Cardiomyopathies - pathology
Cardiomyopathy
Diastolic function
Fibrosis
Heart failure
Heart Failure - genetics
Heart Failure - metabolism
Heart Failure - pathology
Interleukin-1
Male
Mice
Mice, Inbred C57BL
Receptors, Interleukin-1 Type I - metabolism
Stroke Volume - physiology
Ventricular Dysfunction, Left - genetics
Ventricular Dysfunction, Left - metabolism
Ventricular Dysfunction, Left - pathology
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Summary:•Aging promotes diastolic dysfunction and fibrosis.•Genetic deletion of the IL-1RI protected mice from age-associated diastolic dysfunction.•IL-1RI deficiency mitigates interstitial myocardial fibrosis.•Interleukin-1 signaling promotes the development of aging-associated cardiomyopathy. Aging is associated with metabolic and structural changes causing heart failure with preserved ejection fraction (HFpEF). Interleukin-1 (IL-1) is a pro-inflammatory cytokine involved in aging-related inflammation. We sought to determine whether IL-1 mediates aging-related changes in the heart, as seen in HFpEF. We studied age-matched young (4-month-old), middle-aged (14-month-old), and old (23-month-old) wild-type (WT) C57BL/6J and IL-1 receptor type I deficient (IL1RI-KO) male mice. Echocardiography was used to evaluate left ventricular (LV) dimensions and systolic/diastolic function, and a pressure transducer was used to measure the LV end-diastolic pressure. Picrosirius red stain was used to assess for myocardial interstitial fibrosis (MIF) at pathology. WT and IL-1RIKO mice showed a normal cardiac phenotype at young age, without any differences between the two groups. With aging, the WT mice developed LV concentric hypertrophy (as measured by a significant increase in LV mass [+42%, P 
ISSN:1043-4666
1096-0023
DOI:10.1016/j.cyto.2022.155811