Leptin induces cardiac fibrosis through galectin-3, mTOR and oxidative stress

Martínez‐Martínez, Ernesto; Jurado-López, Raquel; Valero-Muñoz, María; Bartolomé, María Visitación; Ballesteros, Sandra; Luaces, María; Briones, Ana M.; López‐Andrés, Natalia; Miana, María; Cachofeiro, Victoria

doi:10.1097/hjh.0000000000000149

Cited by 111 publications

(91 citation statements)

References 64 publications

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“…In this study, MA from HFD show augmented content of type I collagen, which comprises 60% of the vascular wall collagens 51 , without changes in type III collagen. Similar findings have been described in conduit arteries from a Wistar rat DIO model 52 .…”

Section: Discussionsupporting

confidence: 76%

Arterial stiffness is associated with adipokine dysregulation in non-hypertensive obese mice

Gil‐Ortega

Martín-Ramos

Arribas

et al. 2016

Vascular Pharmacology

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Section: Discussionsupporting

confidence: 76%

Arterial stiffness is associated with adipokine dysregulation in non-hypertensive obese mice

Gil‐Ortega

Martín-Ramos

Arribas

et al. 2016

Vascular Pharmacology

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“…Galectin-3 inhibition by N-acetylglucosamine reduced leptin-induced collagen I secretion in cardiac fibroblasts, suggesting that the increase in leptin during obesity can lead to cardiac fibrosis, which can be partially inhibited by limiting galectin-3 activity. 48 Similar results were found in an aldosterone-induced vascular fibrosis animal model demonstrating that aldosterone-induced vascular fibrosis was characterized by increased galectin-3 and collagen I expression in vascular smooth muscle cells and aorta. This form of vascular fibrosis was suppressed in galectin-3 knockout mice or mice treated with citrus pectin, a galectin-3 inhibitor.…”

supporting

confidence: 71%

Galectin-3 and Inflammation

Wan

Liu

2016

Glycobiology Insights

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ABSTRACT:Galectins are a family of β-galactoside-binding proteins that share a consensus sequence in the carbohydrate recognition domain (CRD). Galectin-3 is the most widely studied family member and can be found in the cellular cytoplasm and nucleus, as well as extracellularly in various tissues. The 30-kDa molecule contains an N-terminal proline-rich domain that is important for its oligomerization and a C-terminal CRD for carbohydrate-binding activity. Many studies have shown that galectin-3 may regulate inflammation through a variety of mechanisms. Endogenous galectin-3 has been shown to be involved in the pathogenesis of various diseases, such as fibrosis in the lung, liver, and heart, diabetes mellitus, coronary artery disease, and allergic diseases. In this review, we briefly discuss the pro-or anti-inflammatory roles, as well as potential clinical implications of galectin-3 in these disorders.

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“…The molecular mechanisms responsible for the mTOR‐dependent activation of NOX and NF‐κB in response to BCAA are unknown and this is a limitation of our study. However, other authors have also found a role for mTOR in oxidative stress generation40, 41 or NF‐κB activation in response to different stimuli or pathological conditions 42, 43. Besides mTORC1, BCAA trigger several signalling responses via the activation of AMPK, which plays a role in cellular energy homoeostasis.…”

Section: Discussionmentioning

confidence: 99%

Branched‐chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation

Zhenyukh

González‐Amor

Rodrigues-Díez

et al. 2018

J Cellular Molecular Medi

112

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Branched‐chain amino acids (BCAA: leucine, isoleucine and valine) are essential amino acids implicated in glucose metabolism and maintenance of correct brain function. Elevated BCAA levels can promote an inflammatory response in peripheral blood mononuclear cells. However, there are no studies analysing the direct effects of BCAA on endothelial cells (ECs) and its possible modulation of vascular function. In vitro and ex vivo studies were performed in human ECs and aorta from male C57BL/6J mice, respectively. In ECs, BCAA (6 mmol/L) increased eNOS expression, reactive oxygen species production by mitochondria and NADPH oxidases, peroxynitrite formation and nitrotyrosine expression. Moreover, BCAA induced pro‐inflammatory responses through the transcription factor NF‐κB that resulted in the release of intracellular adhesion molecule‐1 and E‐selectin conferring endothelial activation and adhesion capacity to inflammatory cells. Pharmacological inhibition of mTORC1 intracellular signalling pathway decreased BCAA‐induced pro‐oxidant and pro‐inflammatory effects in ECs. In isolated murine aorta, BCAA elicited vasoconstrictor responses, particularly in pre‐contracted vessels and after NO synthase blockade, and triggered endothelial dysfunction, effects that were inhibited by different antioxidants, further demonstrating the potential of BCAA to induce oxidative stress with functional impact. In summary, we demonstrate that elevated BCAA levels generate inflammation and oxidative stress in ECs, thereby facilitating inflammatory cells adhesion and endothelial dysfunction. This might contribute to the increased cardiovascular risk observed in patients with elevated BCAA blood levels.

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Leptin induces cardiac fibrosis through galectin-3, mTOR and oxidative stress

Cited by 111 publications

References 64 publications

Arterial stiffness is associated with adipokine dysregulation in non-hypertensive obese mice

Arterial stiffness is associated with adipokine dysregulation in non-hypertensive obese mice

Galectin-3 and Inflammation

Branched‐chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation

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