Intermedin ameliorates atherosclerosis in apoE null mice by modifying lipid profiles

Zhang, Xin; Gu, Lunda; Chen, Xiaoping; Wang, Si; Deng, Xiaoming; Liu, Kai; Lv, Zhengbing; Yang, Rui; He, Sen; Peng, Yong; Huang, Dejia; Jiang, Wei; Wu, Kai

doi:10.1016/j.peptides.2012.07.011

Cited by 23 publications

(16 citation statements)

References 19 publications

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“…ADM2/IMD 1–53 inhibits macrophage foam cell formation through decreasing the uptake of modified LDLs by CD36 and class A scavenger receptor (Dai et al , ; Dai et al , ). Another study also showed that ADM2 improved atherosclerosis by increasing plasma HDL cholesterol and decreasing plasma total and LDL cholesterol levels in high‐fat diet‐fed ApoE −/− mice (Zhang et al , ).…”

Section: Adm2 and Cardiometabolic Diseasesmentioning

confidence: 96%

Adrenomedullin 2/intermedin: a putative drug candidate for treatment of cardiometabolic diseases

Zhang

Wang

2017

British J Pharmacology

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Adrenomedullin (ADM) 2/intermedin (IMD) is a short peptide that belongs to the CGRP superfamily. Although it shares receptors with CGRP, ADM and amylin, ADM2 has significant and unique functions in the cardiovascular system. In the past decade, the cardiovascular effect of ADM2 has been carefully analysed. In this review, progress in understanding the effects of ADM2 on the cardiovascular system and its protective role in cardiometabolic diseases are summarized. LINKED ARTICLESThis article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc Abbreviations AAC, abdominal aortic constriction; ACS, acute coronary syndrome; ADM, adrenomedullin; AMPK, AMP-activated protein kinase; AMY, amylin; CRLR, calcitonin receptor-like receptor; ER, endoplasmic reticulum; I/R, ischaemia/reperfusion; RAMP, receptor activity-modifying protein; SHR, spontaneously hypertensive rat; TAC, transverse aortic contraction; VSMC, vascular smooth muscle cell Takei et al., 2004). It is one of the members of the ADM family which are all found in fish but, in mammals, only three peptides -ADM, ADM2 and ADM5 -have been found (Takei et al., 2008). These ADM peptides are themselves a part of the CGRP superfamily. ADM2 is also called intermedin (IMD), owing to its high expression in the intermediate lobe of the pituitary. Both terms, 'ADM2' and 'IMD', are widely used in the literature. However, because IMD was used as the former name for α-melanocyte stimulating hormone, we will use the terms ADM2, ADM2/IMD 1-53 , ADM2/IMD 1-47 and ADM2/IMD 1-40 in this review to avoid confusion. ADM2 shares receptors with CGRP, ADM and amylin (AMY) (Hay et al., 2005) and is widely expressed throughout the body. Recently, progress has been made on the physiological roles of ADM2 in cardiovascular homeostasis and as a protective agent against cardiometabolic diseases. In this review, the structure and expression of ADM2 and the pharmacology of ADM2, in the context of the cardiovascular system and cardiometabolic diseases, are summarized. ADM2 and ADM2 receptorsThe structure of ADM2The Adm2 gene is located on the distal arm of human chromosome 22q13.33 and encodes a pre-pro-peptide containing 148 amino acid residues with a signal sequence at the N terminus . ADM2 belongs to the CGRP superfamily, which includes α-CGRP, β-CGRP, calcitonin receptor-stimulating peptide, AMY, ADM and ADM5 (Hong et al., 2012). ADM2 shares the same structural characteristics with the other family members, including an intramolecular ring of six amino acids residues flanked by a disulfide bond and a putative amidation signal at the C terminus .Sequence alignment has shown that ADM2 shares only 28% sequence identity with its closest paralogue, ADM.However, ADM2 is highly conserved in the orthologues of different species. The mature human ADM2 shares over 60% similarity with fish and 87% identity with the rodent peptides . The property of high con...

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Section: Adm2 and Cardiometabolic Diseasesmentioning

confidence: 96%

Adrenomedullin 2/intermedin: a putative drug candidate for treatment of cardiometabolic diseases

Zhang

Wang

2017

British J Pharmacology

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“…36 The protective effect of IMD on AAA might be partly through beneficially modifying the circulating lipid profile. As to the model of Ang II-induced AAA in ApoE −/− mice, Ang II was the main factor that accelerated the formation of AAA by promoting vascular inflammation, oxidative stress, atherosclerosis, and increased vascular stiffness without altering serum cholesterol concentrations or distribution of lipoprotein cholesterol.…”

Section: Discussionmentioning

confidence: 99%

Intermedin ₁₋ ₅₃ Attenuates Abdominal Aortic Aneurysm by Inhibiting Oxidative Stress

Jia

et al. 2016

ATVB

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Objective-Oxidative stress plays a critical role in the development of abdominal aortic aneurysm (AAA). Intermedin (IMD) is a regulator of oxidative stress. Here, we investigated whether IMD reduces AAA by inhibiting oxidative stress. Approach and Results-In angiotensin II-induced ApoE −/− mouse and CaCl 2 -induced C57BL/6J mouse model of AAA, IMD 1−53 significantly reduced the incidence of AAA and maximal aortic diameter. Ultrasonography, hematoxylin, and eosin staining and Verhoeff-van Gieson staining showed that IMD 1−53 significantly decreased the enlarged aortas and elastic lamina degradation induced by angiotensin II or CaCl 2 . Mechanistically, IMD 1−53 attenuated oxidative stress, inflammation, vascular smooth muscle cell apoptosis, and matrix metalloproteinase activation. IMD 1−53 inhibited the activation of redox-sensitive signaling pathways, decreased the mRNA and protein expression of nicotinamide adenine dinucleotide phosphate oxidase subunits, and reduced the activity of nicotinamide adenine dinucleotide phosphate oxidase in AAA mice. Expression of Nox4 was upregulated in human AAA segments and in angiotensin II-treated mouse aortas and was markedly decreased by IMD 1−53 . In vitro, vascular smooth muscle cells with small-interfering RNA knockdown of IMD showed significantly increased angiotensin II-induced reactive oxygen species, and small-interfering RNA knockdown of Nox4 markedly inhibited the reactive oxygen species. IMD knockdown further increased the apoptosis of vascular smooth muscle cells and inflammation, which was reversed by Nox4 knockdown. Preincubation with IMD 17−47 and protein kinase A inhibitor H89 inhibited the effect of IMD 1-53 , reducing Nox4 protein levels. Conclusions-IMD

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“…Pretreatment with IMD for six weeks prevented the progression of atherosclerotic lesions and the increase in wall thickness in the aorta [35]. Oil-red O staining of the entire aorta and the atherosclerotic aortic root section showed 2-fold decrease of atherogenic plaque.…”

Section: Imd and Atherosclerosismentioning

confidence: 93%

Intermedin/adrenomedullin2: an autocrine/paracrine factor in vascular homeostasis and disease

Zhang

Tang

et al. 2014

Sci. China Life Sci.

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Intermedin (IMD) or adrenomedullin 2 is a novel peptide related to the calcitonin gene-related peptide (CGRP) family. Via calcitonin receptor-like receptor/receptor activity modifying proteins, the common receptor complexes of CGRP, IMD exerts a wide range of biological effects, especially regulation of cardiovascular homeostasis. Proteolytic processing of a larger IMD precursor yields a series of biologically active C-terminal fragments, IMD1-53, IMD1-47 and IMD8-47. IMD and its receptors are present in the cardiovascular system, and IMD is present at low levels in plasma. In the cardiovascular system, IMD has multiple functions such as regulation of blood pressure and cardiac function, pro-angiogenesis, endothelial barrier function protection, anti-oxidative stress, and anti-endoplasmic reticulum stress. IMD participates widely in the pathogenesis of atherosclerosis, hypertension, pulmonary arterial hypertension and vascular calcification. It is a vascular regulatory factor of homeostasis and a vital endogenous protective factor against vascular diseases. intermedin, vessel, homeostasis, vascular diseases Citation:Ni XQ, Zhang JS, Tang CS, Qi YF. Intermedin/adrenomedullin2: an autocrine/paracrine factor in vascular homeostasis and disease. Sci China Life Sci, 2014, 57: 781 -789,

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Intermedin ameliorates atherosclerosis in apoE null mice by modifying lipid profiles

Cited by 23 publications

References 19 publications

Adrenomedullin 2/intermedin: a putative drug candidate for treatment of cardiometabolic diseases

Adrenomedullin 2/intermedin: a putative drug candidate for treatment of cardiometabolic diseases

Intermedin ₁₋ ₅₃ Attenuates Abdominal Aortic Aneurysm by Inhibiting Oxidative Stress

Intermedin/adrenomedullin2: an autocrine/paracrine factor in vascular homeostasis and disease

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Intermedin ameliorates atherosclerosis in apoE null mice by modifying lipid profiles

Cited by 23 publications

References 19 publications

Adrenomedullin 2/intermedin: a putative drug candidate for treatment of cardiometabolic diseases

Adrenomedullin 2/intermedin: a putative drug candidate for treatment of cardiometabolic diseases

Intermedin 1− 53 Attenuates Abdominal Aortic Aneurysm by Inhibiting Oxidative Stress

Intermedin/adrenomedullin2: an autocrine/paracrine factor in vascular homeostasis and disease

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Intermedin ₁₋ ₅₃ Attenuates Abdominal Aortic Aneurysm by Inhibiting Oxidative Stress