Heart remodeling produced by aortic stenosis promotes cardiomyocyte apoptosis mediated by collagen V imbalance

Sant’Ana, Paula Grippa; Batah, Sabrina Setembre; Leao, Patrícia; Teodoro, Walcy Rosolia; Souza, Sérgio Luiz Borges de; Mota, Gustavo Augusto Ferreira; Vileigas, Danielle Fernandes; Silva, Vítor Loureiro da; Campos, Dijon Henrique Salomé de; Okoshi, Katashi; Capelozzi, Vera Luíza; Cicogna, Antônio Carlos; Fabro, Alexandre Todorovic

doi:10.1016/j.pathophys.2018.07.001

Cited by 13 publications

(18 citation statements)

References 27 publications

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“…We found that HIF-1α increased in all groups with heart disease, with an important increase during CR progression, especially in the HF phase. High levels of HIF-1α, resulting from a decrease in its degradation in the presence of tissue hypoxia [ 5 , 20 , 21 , 22 ], may be due to the imbalance between the supply and consumption of O 2 by the myocardium due to disharmony in the proliferative capacity of the capillary network, vascular rarefaction, the degree of concentric hypertrophy, and myocardial fibrosis [ 23 , 24 , 25 , 26 , 27 ]. The accentuation seen over time of these myocardial structural changes may have been responsible for increasing HIF-1α in the different phases of aortic stenosis.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Inducible Factor 1-Alpha and Glucose Metabolism during Cardiac Remodeling Progression from Hypertrophy to Heart Failure

Sant’Ana

Tomasi

Murata

et al. 2023

IJMS

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In pathological cardiac hypertrophy, the heart is more dependent on glucose than fatty acids. This shift in energy metabolism occurs due to several factors, including the oxygen deficit, which activates hypoxia-inducible factor-1α (HIF-1α), a critical molecule related to glucose metabolism. However, there are gaps regarding the behavior of key proteins in the glycolytic pathway and HIF-1α during the transition from hypertrophy to heart failure (HF). This study assesses the hypothesis that there is an early change and enhancement of HIF-1α and the glycolytic pathway, as well as an association between them during cardiac remodeling. Sham and aortic stenosis Wistar rats were analyzed at 2, 6, and 18 weeks and in HF (n = 10–18). Cardiac structure and function were investigated by echocardiogram. Myocardial glycolysis, the aerobic and anaerobic pathways and glycogen were analyzed by enzymatic assay, Western blot, and enzyme-linked immunosorbent assay (ELISA). The following were observed: increased left ventricular hypertrophy; early diastolic function change and severe systolic and diastolic dysfunction in HF; increased HIF-1α in the 2nd week and in HF; precocious alteration and intensification of glycolysis with a shift to anaerobic metabolism from the 6th week onwards; association between HIF-1α, glycolysis, and the anaerobic pathway. Our hypothesis was confirmed as there was an early change and intensification in glucose metabolism, alteration in HIF-1α, and an association between data during the progression from hypertrophy to heart failure.

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Section: Discussionmentioning

confidence: 99%

Hypoxia-Inducible Factor 1-Alpha and Glucose Metabolism during Cardiac Remodeling Progression from Hypertrophy to Heart Failure

Sant’Ana

Tomasi

Murata

et al. 2023

IJMS

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“…In-vivo cardiac function and morphology were measured at 18 and 28 weeks post-surgery via echocardiography (Vivid S6, General Electric Medical Systems, Tirat Carmel, Israel) using a 5.0 ± 11.5 MHz multifrequency transducer, in according to previous studies [23,42]. All examinations were performed blindly by a cardiologist and specialist in echocardiography.…”

Section: Echocardiographic Studymentioning

confidence: 99%

“…Ascending aortic stenosis in young rats has been used to study persistent and chronic pressure overload [22,23]. Cardiac dysfunction induced by this experimental model occurs gradually, resembling the development of the disease in humans.…”

Section: Introductionmentioning

confidence: 99%

Adjustments in β-Adrenergic Signaling Contribute to the Amelioration of Cardiac Dysfunction by Exercise Training in Supravalvular Aortic Stenosis

Souza

Mota

Silva

et al. 2020

Cell Physiol Biochem

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“…The total collagenous fibers in the periadventitial layer of small and median arteries were identified by the picrosirius-polarization method according to previous work [25][26][27][28]. Type I (Col I), III (Col III), and V (Col V) collagen fibers were characterized by immunofluorescence according to our laboratory protocol [28][29][30][31]. Briefly, lung sections (3-4 μm) were dewaxed in xylol, hydrated in graded ethanol, and incubated overnight at 4 ° C with rabbit polyclonal anti-human Col I (1: 700, Rockland), anti-human Col V (1:…”

Section: Histology Immunofluorescence Immunohistochemistry and Mormentioning

confidence: 99%

In situ Evidence of Collagen V and Interleukin-6/Interleukin-17 Activation in Vascular Remodeling of Experimental Pulmonary Hypertension

et al. 2020

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Several studies have reported the pathophysiologic and molecular mechanisms responsible for pulmonary arterial hypertension (PAH). However, the in situ evidence of collagen V (Col V) and interleukin-17 (IL-17)/interleukin-6 (IL-6) activation in PAH has not been fully elucidated. We analyzed the effects of collagen I (Col I), Col V, IL-6, and IL-17 on vascular remodeling and hemodynamics and its possible mechanisms of action in monocrotaline (MCT)-induced PAH. Twenty male Wistar rats were randomly divided into two groups. In the PAH group, animals received MCT 60 mg/kg intraperitoneally, whereas the control group (CTRL) received saline. On day 21, the pulmonary blood pressure (PAP) and right ventricular systolic pressure (RVSP) were determined. Lung histology (smooth muscle cell proliferation [α-smooth muscle actin; α-SMA] and periadventitial fibrosis), immunofluorescence (Col I, Col V, and α-SMA), immunohistochemistry (IL-6, IL-17, and transforming growth factor-beta [TGF-β]), and transmission electron microscopy to detect fibronexus were evaluated. The RVSP (40 ± 2 vs. 24 ± 1 mm Hg, respectively; <i>p</i> < 0.0001), right ventricle hypertrophy index (65 ± 9 and 25 ± 5%, respectively; <i>p</i> < 0.0001), vascular periadventitial Col I and Col V, smooth muscle cell α-SMA+, fibronexus, IL-6, IL-17, and TGF-β were higher in the MCT group than in the CTRL group. In conclusion, our findings indicate in situ evidence of Col V and IL-6/IL-17 activation in vascular remodeling and suggest that increase of Col V may yield potential therapeutic targets for treating patients with PAH.

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Heart remodeling produced by aortic stenosis promotes cardiomyocyte apoptosis mediated by collagen V imbalance

Cited by 13 publications

References 27 publications

Hypoxia-Inducible Factor 1-Alpha and Glucose Metabolism during Cardiac Remodeling Progression from Hypertrophy to Heart Failure

Hypoxia-Inducible Factor 1-Alpha and Glucose Metabolism during Cardiac Remodeling Progression from Hypertrophy to Heart Failure

Adjustments in β-Adrenergic Signaling Contribute to the Amelioration of Cardiac Dysfunction by Exercise Training in Supravalvular Aortic Stenosis

In situ Evidence of Collagen V and Interleukin-6/Interleukin-17 Activation in Vascular Remodeling of Experimental Pulmonary Hypertension

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