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Remote transplantation of human adipose-derived stem cells induces regression of cardiac hypertrophy by regulating the macrophage polarization in spontaneously hypertensive rats.

ABSTRACT: Left ventricular hypertrophy (LVH) in hypertension has prognostic significance on cardiovascular mortality and morbidity. Recently, we have shown that n-butylidenephthalide (BP) improves human adipose-derived stem cell (hADSC) engraftment via attenuated reactive oxygen species (ROS) production. This prompted us to investigate whether remote transplantation of BP-pretreated hADSCs confers attenuated LVH at an established phase of hypertension. Male spontaneously hypertensive rats (SHRs) aged 12 weeks were randomly allocated to receive right hamstring injection of vehicle, clinical-grade hADSCs, and BP-preconditioned hADSCs for 8 weeks. As compared with untreated SHRs, naïve hADSCs decreased the ratio of LV weight to tibia, cardiomyocyte cell size, and collagen deposition independent of hemodynamic changes. These changes were accompanied by attenuated myocardial ROS production and increased p-STAT3 levels. Compared with naïve hADSCs, BP-preconditioned hADSCs provided a further decrease of ROS and LVH and an increase of local hADSC engraftment, STAT3 phosphorylation, STAT3 activity, STAT3 nuclear translocation, myocardial IL-10 levels, and the percentage of M2 macrophage infiltration. SIN-1 or S3I-201 reversed the effects of BP-preconditioned ADSCs increase on myocardial IL-10 levels. Furthermore, SIN-1 abolished the phosphorylation of STAT3, whereas superoxide levels were not affected following the inhibition of STAT3. Our results highlighted the feasibility of remote transplantation of hADSCs can be considered as an alternative procedure to reverse cardiac hypertrophy even at an established phase of hypertension. BP-pretreated hADSCs polarize macrophages into M2 immunoregulatory cells more efficiently than naïve hADSCs via ROS/STAT3 pathway.

SUBMITTER: Lee TM

PROVIDER: S-EPMC6859583 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Remote transplantation of human adipose-derived stem cells induces regression of cardiac hypertrophy by regulating the macrophage polarization in spontaneously hypertensive rats.

Lee Tsung-Ming TM Harn Horng-Jyh HJ Chiou Tzyy-Wen TW Chuang Ming-Hsi MH Chen Chun-Hung CH Chuang Chi-Hsuan CH Lin Po-Cheng PC Lin Shinn-Zong SZ

Redox biology 20190321

Left ventricular hypertrophy (LVH) in hypertension has prognostic significance on cardiovascular mortality and morbidity. Recently, we have shown that n-butylidenephthalide (BP) improves human adipose-derived stem cell (hADSC) engraftment via attenuated reactive oxygen species (ROS) production. This prompted us to investigate whether remote transplantation of BP-pretreated hADSCs confers attenuated LVH at an established phase of hypertension. Male spontaneously hypertensive rats (SHRs) aged 12 w ...[more]

PMID: 31164286

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Project description:Full Title: Transition from Compensated Hypertrophy to Systolic Heart Failure in the Spontaneously Hypertensive Rat: Structure, Function, and Transcript Analysis Gene expression changes and left ventricular remodeling associated with the transition to systolic heart failure (HF) were determined in the spontaneously hypertensive rat (SHR). By combining transcriptomics of left ventricles from six SHR with HF with changes in function and structure we aimed to better understand the molecular events underlying the onset of systolic HF compared to six age-matched, SHR with compensated hypertrophy. Left ventricle (LV) ejection fraction was depressed (82±4 to 52±3 %) in compensated vs. failing animals. Systolic blood pressure decreased and LV end-diastolic and systolic volume increased with HF. Failing SHR hearts also demonstrated increases in left and right ventricular mass relative to non-failing SHRs. LV papillary muscle force development and shortening velocity decreased, β-adrenergic responsiveness was depressed, myocardial stiffness and myocardial fibrosis increased with HF relative to non-failing animals. Initial micro-array analysis revealed that 1,431 transcripts were differentially expressed with HF compared to non-failing SHR (p<0.05). Of the identified transcripts, lipopolysaccharide binding protein, the most highly expressed transcript with HF, was negatively correlated to myocardial force while elevated expression of the collagen cross-linking enzyme lysyl oxidase correlated positively with muscle stiffness. Besides these individual transcripts, gene set enrichment analysis (GSEA) identified multiple enriched pathways with HF, most prominent of the altered signaling pathways involved TGF-β and insulin signaling. GESA analysis additionally identified altered gene sets involving inflammation, oxidative stress, cell degradation and cell death, among others (all p<0.01). In contrast to diastolic HF where few transcripts are reported to be altered, our data indicate multiple genes and pathways involved in a variety of biological processes characterize the onset of systolic HF, consistent with many functional and structural changes present in the failing hypertensive heart.

Dataset Information

Remote transplantation of human adipose-derived stem cells induces regression of cardiac hypertrophy by regulating the macrophage polarization in spontaneously hypertensive rats.

Publications

Remote transplantation of human adipose-derived stem cells induces regression of cardiac hypertrophy by regulating the macrophage polarization in spontaneously hypertensive rats.

Similar Datasets

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