Humanin prevents intra-renal microvascular remodeling and inflammation in hypercholesterolemic ApoE deficient mice

Xin Zhang, Victor H. Urbieta-Caceres, Alfonso Eirin, Caitlin C. Bell, John A. Crane, Hui Tang, Kyra L. Jordan, Yun Kyu Oh, Xiang Yang Zhu, Michael J. Korsmo, Adi R. Bachar, Pinchas Cohen, Amir Lerman, Lilach O Lerman

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Aims: Humanin (HN) is an endogenous mitochondrial-derived cytoprotective peptide that has shown protective effects against atherosclerosis and is expressed in human vessels. However, its effects on the progression of kidney disease are unknown. We hypothesized that HN would protect the kidney in the early phase of atherogenesis. Main methods: Forty-eight mice were studied in four groups (n = 12 each). Twenty-four ApoE deficient mice were fed a 16-week high-cholesterol diet supplemented with saline or HN (4 mg/kg/day, intraperitoneal). C57BL/6 mice were fed a normal diet supplemented with saline or HN. Microvascular architecture was assessed with micro-CT and vascular wall remodeling by alpha-SMA staining. The effects of HN on angiogenesis, inflammation, apoptosis and fibrosis were evaluated in the kidney tissue by Western blotting and histology. Key findings: Cortical microvascular spatial density and media/lumen area ratio were significantly increased in high-cholesterol diet fed ApoE deficient mice, but restored by HN. HN up-regulated the renal expressions of anti-angiogenic proteins angiostatin and TSP-1, and inhibited angiopoietin-1. HN attenuated inflammation by down-regulating MCP-1, TNF-alpha and osteopontin. HN also tended to restore pSTAT3 and attenuated Bax expression, suggesting blunted apoptosis. Kidney collagen IV expression was alleviated by HN treatment. Significance: HN attenuates renal microvascular remodeling, inflammation and apoptosis in the early stage of kidney disease in hypercholesterolemic ApoE -/- mice. HN may serve as a novel therapeutic target to mitigate kidney damage in early atherosclerosis.

Original languageEnglish (US)
Pages (from-to)199-206
Number of pages8
JournalLife Sciences
Volume91
Issue number5-6
DOIs
StatePublished - Sep 4 2012

Fingerprint

Apolipoproteins E
Inflammation
Kidney
Nutrition
Atherosclerosis
Kidney Diseases
Apoptosis
Diet
humanin
Angiogenic Proteins
Angiostatins
Cholesterol
Angiopoietin-1
Thrombospondin 1
Osteopontin
Histology
Inbred C57BL Mouse
Fibrosis
Collagen
Tumor Necrosis Factor-alpha

Keywords

  • Angiogenesis
  • Humanin
  • Hypercholesterolemia
  • Inflammation
  • Kidney disease

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Humanin prevents intra-renal microvascular remodeling and inflammation in hypercholesterolemic ApoE deficient mice. / Zhang, Xin; Urbieta-Caceres, Victor H.; Eirin, Alfonso; Bell, Caitlin C.; Crane, John A.; Tang, Hui; Jordan, Kyra L.; Oh, Yun Kyu; Zhu, Xiang Yang; Korsmo, Michael J.; Bachar, Adi R.; Cohen, Pinchas; Lerman, Amir; Lerman, Lilach O.

In: Life Sciences, Vol. 91, No. 5-6, 04.09.2012, p. 199-206.

Research output: Contribution to journalArticle

Zhang, X, Urbieta-Caceres, VH, Eirin, A, Bell, CC, Crane, JA, Tang, H, Jordan, KL, Oh, YK, Zhu, XY, Korsmo, MJ, Bachar, AR, Cohen, P, Lerman, A & Lerman, LO 2012, 'Humanin prevents intra-renal microvascular remodeling and inflammation in hypercholesterolemic ApoE deficient mice', Life Sciences, vol. 91, no. 5-6, pp. 199-206. https://doi.org/10.1016/j.lfs.2012.07.010
Zhang, Xin ; Urbieta-Caceres, Victor H. ; Eirin, Alfonso ; Bell, Caitlin C. ; Crane, John A. ; Tang, Hui ; Jordan, Kyra L. ; Oh, Yun Kyu ; Zhu, Xiang Yang ; Korsmo, Michael J. ; Bachar, Adi R. ; Cohen, Pinchas ; Lerman, Amir ; Lerman, Lilach O. / Humanin prevents intra-renal microvascular remodeling and inflammation in hypercholesterolemic ApoE deficient mice. In: Life Sciences. 2012 ; Vol. 91, No. 5-6. pp. 199-206.
@article{80ebb84cd9624198a8565482cdad5da6,
title = "Humanin prevents intra-renal microvascular remodeling and inflammation in hypercholesterolemic ApoE deficient mice",
abstract = "Aims: Humanin (HN) is an endogenous mitochondrial-derived cytoprotective peptide that has shown protective effects against atherosclerosis and is expressed in human vessels. However, its effects on the progression of kidney disease are unknown. We hypothesized that HN would protect the kidney in the early phase of atherogenesis. Main methods: Forty-eight mice were studied in four groups (n = 12 each). Twenty-four ApoE deficient mice were fed a 16-week high-cholesterol diet supplemented with saline or HN (4 mg/kg/day, intraperitoneal). C57BL/6 mice were fed a normal diet supplemented with saline or HN. Microvascular architecture was assessed with micro-CT and vascular wall remodeling by alpha-SMA staining. The effects of HN on angiogenesis, inflammation, apoptosis and fibrosis were evaluated in the kidney tissue by Western blotting and histology. Key findings: Cortical microvascular spatial density and media/lumen area ratio were significantly increased in high-cholesterol diet fed ApoE deficient mice, but restored by HN. HN up-regulated the renal expressions of anti-angiogenic proteins angiostatin and TSP-1, and inhibited angiopoietin-1. HN attenuated inflammation by down-regulating MCP-1, TNF-alpha and osteopontin. HN also tended to restore pSTAT3 and attenuated Bax expression, suggesting blunted apoptosis. Kidney collagen IV expression was alleviated by HN treatment. Significance: HN attenuates renal microvascular remodeling, inflammation and apoptosis in the early stage of kidney disease in hypercholesterolemic ApoE -/- mice. HN may serve as a novel therapeutic target to mitigate kidney damage in early atherosclerosis.",
keywords = "Angiogenesis, Humanin, Hypercholesterolemia, Inflammation, Kidney disease",
author = "Xin Zhang and Urbieta-Caceres, {Victor H.} and Alfonso Eirin and Bell, {Caitlin C.} and Crane, {John A.} and Hui Tang and Jordan, {Kyra L.} and Oh, {Yun Kyu} and Zhu, {Xiang Yang} and Korsmo, {Michael J.} and Bachar, {Adi R.} and Pinchas Cohen and Amir Lerman and Lerman, {Lilach O}",
year = "2012",
month = "9",
day = "4",
doi = "10.1016/j.lfs.2012.07.010",
language = "English (US)",
volume = "91",
pages = "199--206",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",
number = "5-6",

}

TY - JOUR

T1 - Humanin prevents intra-renal microvascular remodeling and inflammation in hypercholesterolemic ApoE deficient mice

AU - Zhang, Xin

AU - Urbieta-Caceres, Victor H.

AU - Eirin, Alfonso

AU - Bell, Caitlin C.

AU - Crane, John A.

AU - Tang, Hui

AU - Jordan, Kyra L.

AU - Oh, Yun Kyu

AU - Zhu, Xiang Yang

AU - Korsmo, Michael J.

AU - Bachar, Adi R.

AU - Cohen, Pinchas

AU - Lerman, Amir

AU - Lerman, Lilach O

PY - 2012/9/4

Y1 - 2012/9/4

N2 - Aims: Humanin (HN) is an endogenous mitochondrial-derived cytoprotective peptide that has shown protective effects against atherosclerosis and is expressed in human vessels. However, its effects on the progression of kidney disease are unknown. We hypothesized that HN would protect the kidney in the early phase of atherogenesis. Main methods: Forty-eight mice were studied in four groups (n = 12 each). Twenty-four ApoE deficient mice were fed a 16-week high-cholesterol diet supplemented with saline or HN (4 mg/kg/day, intraperitoneal). C57BL/6 mice were fed a normal diet supplemented with saline or HN. Microvascular architecture was assessed with micro-CT and vascular wall remodeling by alpha-SMA staining. The effects of HN on angiogenesis, inflammation, apoptosis and fibrosis were evaluated in the kidney tissue by Western blotting and histology. Key findings: Cortical microvascular spatial density and media/lumen area ratio were significantly increased in high-cholesterol diet fed ApoE deficient mice, but restored by HN. HN up-regulated the renal expressions of anti-angiogenic proteins angiostatin and TSP-1, and inhibited angiopoietin-1. HN attenuated inflammation by down-regulating MCP-1, TNF-alpha and osteopontin. HN also tended to restore pSTAT3 and attenuated Bax expression, suggesting blunted apoptosis. Kidney collagen IV expression was alleviated by HN treatment. Significance: HN attenuates renal microvascular remodeling, inflammation and apoptosis in the early stage of kidney disease in hypercholesterolemic ApoE -/- mice. HN may serve as a novel therapeutic target to mitigate kidney damage in early atherosclerosis.

AB - Aims: Humanin (HN) is an endogenous mitochondrial-derived cytoprotective peptide that has shown protective effects against atherosclerosis and is expressed in human vessels. However, its effects on the progression of kidney disease are unknown. We hypothesized that HN would protect the kidney in the early phase of atherogenesis. Main methods: Forty-eight mice were studied in four groups (n = 12 each). Twenty-four ApoE deficient mice were fed a 16-week high-cholesterol diet supplemented with saline or HN (4 mg/kg/day, intraperitoneal). C57BL/6 mice were fed a normal diet supplemented with saline or HN. Microvascular architecture was assessed with micro-CT and vascular wall remodeling by alpha-SMA staining. The effects of HN on angiogenesis, inflammation, apoptosis and fibrosis were evaluated in the kidney tissue by Western blotting and histology. Key findings: Cortical microvascular spatial density and media/lumen area ratio were significantly increased in high-cholesterol diet fed ApoE deficient mice, but restored by HN. HN up-regulated the renal expressions of anti-angiogenic proteins angiostatin and TSP-1, and inhibited angiopoietin-1. HN attenuated inflammation by down-regulating MCP-1, TNF-alpha and osteopontin. HN also tended to restore pSTAT3 and attenuated Bax expression, suggesting blunted apoptosis. Kidney collagen IV expression was alleviated by HN treatment. Significance: HN attenuates renal microvascular remodeling, inflammation and apoptosis in the early stage of kidney disease in hypercholesterolemic ApoE -/- mice. HN may serve as a novel therapeutic target to mitigate kidney damage in early atherosclerosis.

KW - Angiogenesis

KW - Humanin

KW - Hypercholesterolemia

KW - Inflammation

KW - Kidney disease

UR - http://www.scopus.com/inward/record.url?scp=84865271368&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865271368&partnerID=8YFLogxK

U2 - 10.1016/j.lfs.2012.07.010

DO - 10.1016/j.lfs.2012.07.010

M3 - Article

C2 - 22820173

AN - SCOPUS:84865271368

VL - 91

SP - 199

EP - 206

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

IS - 5-6

ER -