Renal Revascularization Attenuates Myocardial Mitochondrial Damage and Improves Diastolic Function in Pigs with Metabolic Syndrome and Renovascular Hypertension

Farahani, Rahele A.; Yu, Shasha; Ferguson, Christopher M.; Zhu, Xiangyang; Tang, Hui; Jordan, Kyra L.; Saadiq, Ishran M.; Herrmann, Sandra M.; Chade, Alejandro; Lerman, Amir; Lerman, Lilach O.; Eirin, Alfonso

doi:10.1007/s12265-021-10155-3

Cited by 8 publications

(1 citation statement)

References 47 publications

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“…Twenty-three 3-months old female pigs were studied for 16 weeks. At baseline, 17 pigs were fed with a high-cholesterol/high-carbohydrate diet ( 15 ), and on week 6, underwent RAS surgery to induce RVH as described ( 16 ). Briefly, 0.25g tiletamine hydrochloride/zolazepam hydrochloride (Telazol ® , Zoetis, Kalamazoo, MI) and 0.5g xylazine (Xylamed, VetOne, Bimeda-MTC Animal Health, Cambridge, ON, Canada) were used for intramuscular anesthesia, followed by intravenous ketamine (0.2 mg/kg/min, Ketaset, Zoetis, Kalamazoo, MI) and xylazine (0.03 mg/kg/min) for maintenance.…”

Section: Methodsmentioning

confidence: 99%

IL-10 partly mediates the ability of MSC-derived extracellular vesicles to attenuate myocardial damage in experimental metabolic renovascular hypertension

Jiang

Hong²,

Zhu³

et al. 2022

Front. Immunol.

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Extracellular vesicles (EVs) obtain properties of immunomodulation and tissue repair from their parental mesenchymal stem cells (MSCs), and upon delivery may be associated with fewer adverse events. EVs derived from adipose-tissue MSCs restored kidney function by attenuating kidney inflammation in a swine model of metabolic syndrome (MetS) and renal artery stenosis via anti-inflammatory pathways. EVs also ameliorated myocardial injury in renovascular hypertension (RVH) secondary to inflammation in cardiorenal disease, but the mechanisms regulating this effect are unknown. We hypothesize that the anti-inflammatory cytokine interleukin (IL)-10 mediates the reparative effects of EVs on cardiovascular complications in a preclinical swine model with coexisting MetS and RVH. Twenty-three pigs established as Lean controls or RVH models were observed for 16 weeks. At 12 weeks RVH subgroups received an intrarenal delivery of 1011 either wildtype (WT) EVs or EVs after IL-10 knockdown (KD) (RVH+WT-EVs or RVH+IL-10-KD-EVs, respectively). Cardiac and renal function were studied in-vivo and myocardial tissue injury in-vitro 4 weeks later. RVH pigs showed myocardial inflammation, fibrosis, and left ventricular diastolic dysfunction. WT-EVs attenuated these impairments, increased capillary density, and decreased myocardial inflammation in-vivo. In-vitro, co-incubation with IL-10-containing WT-EVs decreased activated T-cells proliferation and endothelial cells inflammation and promoted their migration. Contrarily, these cardioprotective effects were largely blunted using IL-10-KD-EVs. Thus, the anti-inflammatory and pro-angiogenic effects of EVs in RVH may be partly attributed to their cargo of anti-inflammatory IL-10. Early intervention of IL-10-containing EVs may be helpful to prevent cardiovascular complications of MetS concurrent with RVH.

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Section: Methodsmentioning

confidence: 99%

IL-10 partly mediates the ability of MSC-derived extracellular vesicles to attenuate myocardial damage in experimental metabolic renovascular hypertension

Jiang

Hong²,

Zhu³

et al. 2022

Front. Immunol.

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Oxidative stress initiates hemodynamic change in CKD-induced heart disease

Sen,

Hamers,

Sittig

et al. 2024

Basic Res Cardiol

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Chronic kidney disease (CKD) predisposes to cardiac remodeling and coronary microvascular dysfunction. Studies in swine identified changes in microvascular structure and function, as well as changes in mitochondrial structure and oxidative stress. However, CKD was combined with metabolic derangement, thereby obscuring the contribution of CKD alone. Therefore, we studied the impact of CKD on the heart and combined proteome studies with measurement of cardiac function and perfusion to identify processes involved in cardiac remodeling in CKD. CKD was induced in swine at 10–12 weeks of age while sham-operated swine served as controls. 5–6 months later, left ventricular (LV) function and coronary flow reserve were measured. LC–MS–MS-based proteomic analysis of LV tissue was performed. LV myocardium and kidneys were histologically examined for interstitial fibrosis and oxidative stress. Renal embolization resulted in mild chronic kidney injury (increased fibrosis and urinary NGAL). PV loops showed LV dilation and increased wall stress, while preload recruitable stroke work was impaired in CKD. Quantitative proteomic analysis of LV myocardium and STRING pre-ranked functional analysis showed enrichments in pathways related to contractile function, reactive oxygen species, and extracellular matrix (ECM) remodeling, which were confirmed histologically and associated with impaired total anti-oxidant capacity. H2O2 exposure of myocardial slices from CKD, but not normal swine, impaired contractile function. Furthermore, in CKD, mitochondrial proteins were downregulated suggesting mitochondrial dysfunction which was associated with higher basal coronary blood flow. Thus, mild CKD induces alterations in mitochondrial proteins along with contractile proteins, oxidative stress and ECM remodeling, that were associated with changes in cardiac function and perfusion.

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Best Paper of the Year 2021

Xiao

Lara‐Pezzi

2022

J. of Cardiovasc. Trans. Res.

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We are excited to present a new section in JCTR that highlights the best papers of the previous year. The following articles were selected by the associate editors from those accepted during 2021 and based on their relevance, impact, and how they contribute to the Journal's aims. We believe that they showcase the quality and diversity of the papers published in JCTR. Best Paper of the Year-Aged monkeys fed a high-fat/high-sugar diet recapitulate metabolic disorders and cardiac contractile dysfunction, by Shuang Zheng and colleagues [1].

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Renal Revascularization Attenuates Myocardial Mitochondrial Damage and Improves Diastolic Function in Pigs with Metabolic Syndrome and Renovascular Hypertension

Cited by 8 publications

References 47 publications

IL-10 partly mediates the ability of MSC-derived extracellular vesicles to attenuate myocardial damage in experimental metabolic renovascular hypertension

IL-10 partly mediates the ability of MSC-derived extracellular vesicles to attenuate myocardial damage in experimental metabolic renovascular hypertension

Oxidative stress initiates hemodynamic change in CKD-induced heart disease

Best Paper of the Year 2021

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