Biology subjects

Crocini, C.

Publications and source records attributed to Crocini, C..

4 recordsLinked to original sources

bioRxiv2025

Age-Dependent Mechanisms of Cardiac Hypertrophy Regression Following Exercise in Female Mice

Cardiac adaptation to exercise is a fundamental physiological process, but its regression and the underlying molecular mechanisms, particularly in relation to age, remain poorly understood. This study investigated the age-dependent differences in cardiac remodeling and molecular signaling during exercise training and detraining in young (5-week-old) and adult (24-week-old) female mice, focusing specifically on how cardiac plasticity changes with adulthood rather than senescence. While both age groups exhibited significant cardiac hypertrophy after the exercise period, young mice displayed significantly more hypertrophic growth (23% increase in left ventricular mass versus 15% in adults). During detraining, cardiac mass regression occurred more rapidly in young mice. Transcriptomic analysis revealed distinct gene expression profiles between age groups, with changes in metabolic and autophagy pathways. Notably, ERK1/2 phosphorylation increased significantly during exercise in young but not adult hearts, correlating with elevated expression of well-known genes associated with exercise, namely CITED4 and SOD2. Furthermore, increased LC3-II/LC3-I ratio and AMPK phosphorylation were observed exclusively in young mice during detraining, indicating age-specific activation of autophagy-mediated cardiac remodeling. These findings demonstrate that cardiac adaptability to exercise and detraining follows distinct molecular pathways in young versus adult mice, with the younger heart exhibiting greater plasticity through enhanced ERK signaling during hypertrophy and autophagy during regression. This age-dependent cardiac plasticity may have important implications for understanding the cardiovascular benefits of exercise across the lifespan and developing age-appropriate exercise recommendations.

physiology↗

bioRxiv2024

A Conserved Mechanism of Cardiac Hypertrophy Regression through FoxO1

The heart is a highly plastic organ that responds to diverse stimuli to modify form and function. The molecular mechanisms of adaptive physiological cardiac hypertrophy are well-established; however, the regulation of hypertrophy regression is poorly understood. To identify molecular features of regression, we studied Burmese pythons which experience reversible cardiac hypertrophy following large, infrequent meals. Using multi-omics screens followed by targeted analyses, we found forkhead box protein O1 (FoxO1) transcription factor signaling, and downstream autophagy activity, were downregulated during hypertrophy, but re-activated with regression. To determine whether these events were mechanistically related to regression, we established an in vitro platform of cardiomyocyte hypertrophy and regression from treatment with fed python plasma. FoxO1 inhibition prevented regression in this system, while FoxO1 activation reversed fed python plasma-induced hypertrophy in an autophagy-dependent manner. We next examined whether FoxO1 was implicated in mammalian models of reversible hypertrophy from exercise and pregnancy and found that in both cases FoxO1 was activated during regression. In these models, as in pythons, activation of FoxO1 was associated with increased expression FoxO1 target genes involved in autophagy. Taken together, our findings suggest FoxO1-dependent autophagy is a conserved mechanism for regression of physiological cardiac hypertrophy across species. HIGHLIGHTSO_LIPost-prandial cardiac remodeling in Burmese pythons is associated with dynamic regulation of FoxO1 and autophagy. C_LIO_LIRegression of fed python plasma-induced hypertrophy in mammalian cardiomyocytes is FoxO1-dependent. C_LIO_LIActivation of FoxO1-dependent autophagy is a conserved feature of physiological hypertrophy regression in mammalian models. C_LI

physiology↗

bioRxiv2023

Optogenetic confirmation of transverse-tubular membrane excitability in intact cardiac myocytes

T-tubules (TT) form a complex network of sarcolemmal membrane invaginations, essential for well-coordinated excitation-contraction coupling (ECC) and, thus, homogeneous mechanical activation of cardiomyocytes. ECC is initiated by rapid depolarization of the sarcolemmal membrane. Whether TT membrane depolarisation is active (local generation of action potentials; AP) or passive (following depolarisation of the outer cell surface sarcolemma; SS) has not been experimentally assessed in cardiomyocytes. Based on the assessment of ion flux pathways needed for AP generation, we hypothesise that TT are excitable. We therefore explored TT excitability experimentally, using an all-optical approach to stimulate and record trans-membrane potential changes in TT that were electrically insulated from the SS membrane by transient osmotic shock. Our results establish that cardiomyocyte TT can generate AP. These AP show electrical features that differ substantially from those observed in SS, consistent with differences in the density of ion channels and transporters in the two different membrane domains. We propose that TT-generated AP represent a safety mechanism for TT AP propagation and ECC, which may be particularly relevant in pathophysiological settings where morpho-functional changes reduce the electrical connectivity between SS and TT membranes. KEY POINTSO_LICardiomyocytes are characterized by a complex network of membrane invaginations (the T-tubular system) that propagate action potentials to the core of the cell, ensuring synchronous and uniform cell contraction. C_LIO_LIIn this study, we investigate whether the T-tubular system is able to generate action potentials autonomously, rather than following depolarization of the outer cell surface sarcolemma. C_LIO_LIFor this purpose, we developed a fully optical platform to probe and manipulate the electrical dynamics of sub-cellular membrane domains. C_LIO_LIOur findings demonstrate that T-tubules are intrinsically excitable, revealing distinct characteristics of self-generated T-tubular action potentials. C_LIO_LIThis active electrical capability may serve as a protective mechanism against voltage drops occurring within the T-tubular network. C_LI

physiology↗

bioRxiv2020

3D imaging and morphometry of the heart capillary system in spontaneously hypertensive rats and normotensive controls

Systemic arterial hypertension is a highly prevalent chronic disease associated with hypertensive cardiomyopathy. One important feature of this condition is remodelling of intramural small coronary arteries and arterioles. Here, we investigated the implications of this remodelling in the downstream vascular organization, in particular at the capillary level. We used Spontaneously Hypertensive Rats (SHR) exhibiting many features of the human hypertensive cardiomyopathy. We generated 3D high-resolution mesoscopic reconstructions of the entire network of SHR hearts combining gel-based fluorescent labelling of coronaries with a CLARITY-based tissue clearing protocol. We performed morphometric quantification of the capillary network over time to assess capillary diameter, linear density, and angular dispersion. In SHRs, we found significant remodelling of the capillary network density and dispersion. SHR capillary density is increased in both ventricles and at all ages, including before the onset of systemic hypertension. This result suggests that remodelling occurs independently from the onset of systemic hypertension and left ventricular hypertrophy. On the contrary, capillary angular dispersion increases with time in SHR. Consistently, our multi-modal imaging underlined a strong correlation between vascular dispersion and cellular disarray. Together our data show that 3D high-resolution reconstruction of the capillary network can unveil anatomic signatures in both physiological and pathological cardiac conditions, thus offering a reliable method for integrated quantitative analyses.

physiology↗