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Mild dyslipidemia accelerates tumorigenesis through expansion of Ly6C^hi monocytes and differentiation to pro-angiogenic myeloid cells.

ABSTRACT: Cancer and cardiovascular disease (CVD) share common risk factors such as dyslipidemia, obesity and inflammation. However, the role of pro-atherogenic environment and its associated low-grade inflammation in tumor progression remains underexplored. Here we show that feeding C57BL/6J mice with a non-obesogenic high fat high cholesterol diet (HFHCD) for two weeks to induce mild dyslipidemia, increases the pool of circulating Ly6C^hi monocytes available for initial melanoma development, in an IL-1β-dependent manner. Descendants of circulating myeloid cells, which accumulate in the tumor microenvironment of mice under HFHCD, heighten pro-angiogenic and immunosuppressive activities locally. Limiting myeloid cell accumulation or targeting VEGF-A production by myeloid cells decrease HFHCD-induced tumor growth acceleration. Reverting the HFHCD to a chow diet at the time of tumor implantation protects against tumor growth. Together, these data shed light on cross-disease communication between cardiovascular pathologies and cancer.

SUBMITTER: Tran T

PROVIDER: S-EPMC9475043 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Mild dyslipidemia accelerates tumorigenesis through expansion of Ly6C<sup>hi</sup> monocytes and differentiation to pro-angiogenic myeloid cells.

Tran Thi T Lavillegrand Jean-Remi JR Lereverend Cedric C Esposito Bruno B Cartier Lucille L Montabord Melanie M Tran-Rajau Jaouen J Diedisheim Marc M Gruel Nadège N Ouguerram Khadija K Paolini Lea L Lenoir Olivia O Pinteaux Emmanuel E Brabencova Eva E Tanchot Corinne C Urquia Pauline P Lehmann-Che Jacqueline J Le Naour Richard R Merrouche Yacine Y Stockmann Christian C Mallat Ziad Z Tedgui Alain A Ait-Oufella Hafid H Tartour Eric E Potteaux Stephane S

Nature communications 20220914 1

Cancer and cardiovascular disease (CVD) share common risk factors such as dyslipidemia, obesity and inflammation. However, the role of pro-atherogenic environment and its associated low-grade inflammation in tumor progression remains underexplored. Here we show that feeding C57BL/6J mice with a non-obesogenic high fat high cholesterol diet (HFHCD) for two weeks to induce mild dyslipidemia, increases the pool of circulating Ly6C<sup>hi</sup> monocytes available for initial melanoma development, i ...[more]

PMID: 36104342

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Project description:Heme oxygenase-1 (Hmox1) is a stress-inducible protein crucial in heme catabolism. The end products of its enzymatic activity possess anti-oxidative, anti-apoptotic and anti-inflammatory properties. Cardioprotective effects of Hmox1 were demonstrated in experimental models of myocardial infarction (MI). Nevertheless, its importance in timely resolution of post-ischemic inflammation remains incompletely understood. The aim of this study was to determine the role of Hmox1 in the monocyte/macrophage-mediated cardiac remodeling in a mouse model of MI. Hmox1 knockout (Hmox1-/-) and wild-type (WT, Hmox1+/+) mice were subjected to a permanent ligation of the left anterior descending coronary artery. Significantly lower incidence of left ventricle (LV) free wall rupture was noted between 3rd and 5th day after MI in Hmox1-/- mice resulting in their better overall survival. Then, starting from 7th until 21st day post-MI a more potent deterioration of LV function was observed in Hmox1-/- than in the surviving Hmox1+/+ mice. This was accompanied by higher numbers of Ly6Chi monocytes in peripheral blood, as well as higher expression of monocyte chemoattractant protein-1 and adhesion molecules in the hearts of MI-operated Hmox1-/- mice. Consequently, a greater post-MI monocyte-derived myocardial macrophage infiltration was noted in Hmox1-deficient individuals. Splenectomy decreased the numbers of circulating inflammatory Ly6Chi monocytes in blood, reduced the numbers of proinflammatory cardiac macrophages and significantly improved the post-MI LV function in Hmox1-/- mice. In conclusion, Hmox1 deficiency has divergent consequences in MI. On the one hand, it improves early post-MI survival by decreasing the occurrence of cardiac rupture. Afterwards, however, the hearts of Hmox1-deficient mice undergo adverse late LV remodeling due to overactive and prolonged post-ischemic inflammatory response. We identified spleen as an important source of these cardiovascular complications in Hmox1-/- mice.

Dataset Information

Mild dyslipidemia accelerates tumorigenesis through expansion of Ly6C^hi monocytes and differentiation to pro-angiogenic myeloid cells.

Publications

Mild dyslipidemia accelerates tumorigenesis through expansion of Ly6C<sup>hi</sup> monocytes and differentiation to pro-angiogenic myeloid cells.

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Dataset Information

Mild dyslipidemia accelerates tumorigenesis through expansion of Ly6Chi monocytes and differentiation to pro-angiogenic myeloid cells.

Publications

Mild dyslipidemia accelerates tumorigenesis through expansion of Ly6C&lt;sup&gt;hi&lt;/sup&gt; monocytes and differentiation to pro-angiogenic myeloid cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Mild dyslipidemia accelerates tumorigenesis through expansion of Ly6C^hi monocytes and differentiation to pro-angiogenic myeloid cells.

Mild dyslipidemia accelerates tumorigenesis through expansion of Ly6C<sup>hi</sup> monocytes and differentiation to pro-angiogenic myeloid cells.