Diet-induced obese mice are resistant to improvements in cardiac function resulting from short-term adropin treatment

Thapa, Dharendra; Xie, Bingxian; Mushala, Bellina; Zhang, Manling; Manning, Janet R.; Paramesha, Bugga; Stoner, Michael W.; Jurczak, Michael J.; Scott, Iain

doi:10.1016/j.crphys.2022.01.005

Cited by 5 publications

(5 citation statements)

References 14 publications

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“…In addition, the expression of maturation-related cardiac marker gene was investigated. After 5 days of culture, higher expression of electrical coupling-related ( KCNJ2 , GJA1 ) 38 , 39 and metabolic-related genes ( PDK4 , CPT1B , PPARGCLA ) 40 , 41 was found compared to the control tissue (Fig. 3i ), which results were consistent with the morphometric analysis (Fig.…”

Section: Resultssupporting

confidence: 85%

Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities

Mao

Zhang

et al. 2023

Nat Commun

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Recapitulating the complex structural, mechanical, and electrophysiological properties of native myocardium is crucial to engineering functional cardiac tissues. Here, we report a leaf-venation-directed strategy that enables the compaction and remodeling of cell-hydrogel hybrids into highly aligned and densely packed organizations in predetermined patterns. This strategy contributes to interconnected tubular structures with cell alignment along the hierarchical channels. Compared to randomly-distributed cells, the engineered leaf-venation-directed-cardiac tissues from neonatal rat cardiomyocytes manifest advanced maturation and functionality as evidenced by detectable electrophysiological activity, macroscopically synchronous contractions, and upregulated maturation genes. As a demonstration, human induced pluripotent stem cell-derived leaf-venation-directed-cardiac tissues are engineered with evident structural and functional improvement over time. With the elastic scaffolds, leaf-venation-directed tissues are assembled into 3D centimeter-scale cardiac constructs with programmed mechanical properties, which can be delivered through tubing without affecting cell viability. The present strategy may generate cardiac constructs with multifaceted functionalities to meet clinical demands.

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Section: Resultssupporting

confidence: 85%

Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities

Mao

Zhang

et al. 2023

Nat Commun

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“…In ApoE knockout mice, a model of atherosclerosis, adropin decreased atherosclerotic lesion size, reduced aortic monocyte/macrophage infiltration, and decreased VSMC proliferation (36). In healthy mice, three days of adropin administration exerted a moderate improvement on ex vivo cardiac work and output, in addition to increased coronary blood flow (173,184); however, a high-fat diet inhibited adropin-induced cardiac function observed in the lean mice (184). Similar to skeletal muscle and the liver, adropin treatment improved insulin signaling and glucose utilization in cardiomyocytes from healthy mice and modulate substrate utilization (173,184).…”

Section: Vsmcs and Adropinmentioning

confidence: 99%

“…Beyond its well-established metabolic effects, increasing evidence indicates that adropin also exerts cardiovascular effects. For example, adropin has been shown to regulate cardiac energy substrate flexibility (9,173,174,184), promote angiogenesis (8), decrease endothelial inflammation (8,36), activate endothelial nitric oxide (NO) synthase (eNOS) (8), and cause endothelial-dependent vasodilation (170). All this suggests that adropin signaling may be beneficial to the cardiovascular system.…”

Section: Introductionmentioning

confidence: 99%

Role of adropin in arterial stiffening associated with obesity and type 2 diabetes

Jurrissen

Ramirez‐Perez

Cabral-Amador

et al. 2022

American Journal of Physiology-Heart and Circulatory Physiology

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Adropin is a peptide largely secreted by the liver and known to regulate energy homeostasis; however, it also exerts cardiovascular effects. Herein, we tested the hypothesis that low circulating levels of adropin in obesity and type 2 diabetes (T2D) contribute to arterial stiffening. In support of this hypothesis, we report that obesity and T2D is associated with reduced levels of adropin (in liver and plasma) and increased arterial stiffness in mice and humans. Establishing causation, we show that mesenteric arteries from adropin knockout mice are also stiffer, relative to arteries from wild-type counterparts, thus recapitulating the stiffening phenotype observed in T2D db/db mice. Given the above, we performed a set of follow-up experiments, in which we found that: 1) exposure of endothelial cells or isolated mesenteric arteries from db/db mice to adropin reduces filamentous actin (F-actin) stress fibers and stiffness; 2) adropin-induced reduction of F-actin and stiffness in endothelial cells and db/db mesenteric arteries is abrogated by inhibition of nitric oxide (NO) synthase; and 3) stimulation of smooth muscle cells or db/db mesenteric arteries with a NO mimetic reduces stiffness. Last, we demonstrated that in vivo treatment of db/db mice with adropin for four weeks reduces stiffness in mesenteric arteries. Collectively, these findings indicate that adropin can regulate arterial stiffness, likely via endothelial-derived NO, and thus support the notion that "hypoadropinemia" should be considered as a putative target for the prevention and treatment of arterial stiffening in obesity and T2D.

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“… 54 Although short-term administration of adropin may fail to exert a protective effect on cardiac function in obese animals. 55 Besides, adropin could promote eNOS activation and perfusion recovery after hindlimb ischemia by upregulating VEGFR2, 56 suppress proliferation and phenotypic modulation of VSMCs induced by angiotensin II via AMPK/ACC signaling, 46 and attenuate vascular calcification by repressing VSMCs osteogenic differentiation through JAK2/STAT3 signaling, 57 as well as inhibit TNF-α-induced THP1 monocyte adhesion to VECs, prevent macrophages from polarizing into a pro-inflammatory phenotype and reduce the formation of atherosclerotic lesions in apoE −/− mice. 58 Additionally, exposure to cell-free hemoglobin resulted in decreased expressions of adropin and increased paracellular permeability of VECs, and treatment with adropin was able to protect against the hyperpermeability and suppress macrophage trans-endothelial migration.…”

Section: Hepatokinesmentioning

confidence: 99%

Emerging Evidence Linking the Liver to the Cardiovascular System: Liver-derived Secretory Factors

Liu¹,

Shao²,

Han³

et al. 2023

J Clin Transl Hepatol

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Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide. Recently, accumulating evidence has revealed hepatic mediators, termed as liver-derived secretory factors (LDSFs), play an important role in regulating CVDs such as atherosclerosis, coronary artery disease, thrombosis, myocardial infarction, heart failure, metabolic cardiomyopathy, arterial hypertension, and pulmonary hypertension. LDSFs presented here consisted of microbial metabolite, extracellular vesicles, proteins, and microRNA, they are primarily or exclusively synthesized and released by the liver, and have been shown to exert pleiotropic actions on cardiovascular system. LDSFs mainly target vascular endothelial cell, vascular smooth muscle cells, cardiomyocytes, fibroblasts, macrophages and platelets, and further modulate endothelial nitric oxide synthase/nitric oxide, endothelial function, energy metabolism, inflammation, oxidative stress, and dystrophic calcification. Although some LDSFs are known to be detrimental/beneficial, controversial findings were also reported for many. Therefore, more studies are required to further explore the causal relationships between LDSFs and CVDs and uncover the exact mechanisms, which is expected to extend our understanding of the crosstalk between the liver and cardiovascular system and identify potential therapeutic targets. Furthermore, in the case of patients with liver disease, awareness should be given to the implications of these abnormalities in the cardiovascular system. These studies also underline the importance of early recognition and intervention of liver abnormalities in the practice of cardiovascular care, and a multidisciplinary approach combining hepatologists and cardiologists would be more preferable for such patients.

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Diet-induced obese mice are resistant to improvements in cardiac function resulting from short-term adropin treatment

Cited by 5 publications

References 14 publications

Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities

Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities

Role of adropin in arterial stiffening associated with obesity and type 2 diabetes

Emerging Evidence Linking the Liver to the Cardiovascular System: Liver-derived Secretory Factors

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