Restoration of coronary collateral growth in the Zucker obese rat

Impact of VEGF and ecSOD

Naoichiro Hattan, William M. Chilian, Frank Park, Petra Rocic

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The metabolic syndrome (MS), a condition characterized byseveral risk factors for coronary artery disease, including obesity, is associatedwith endothelial dysfunction and oxidative stress. Because proper endothelial function is essential for signaling of certain growth factors (vascularendothelial growth factor, VEGF) we hypothesized that coronary collateral growth (CCG) is impaired in a model of the MS. To test this hypothesis,we stimulated coronary collateral growth in pre-diabetic Zuckerobese fatty rats (OZR) and lean littermates (LZR) by using episodic, repetitive ischemia (RI: 40 s left anterior descending arterial occlusion, 24/d for 14d). Myocardial blood flow (MBF, radioactive microspheres) was measured inthe normal (NZ) and collateral-dependent (ischemic) zones (CZ); CCG was assessed as a ratio of CZ/NZ flow (unity represents complete restoration ofCZ flow). In LZR, CZ/NZ ratio increased from 0.18 ± 0.03 to 0.81± 0.07 afterRI (P < 0.05). In contrast, in OZR rats CZ/NZ did not increase after RI(0.15 ± 0.04 vs 0.18 ± 0.04). To rectify abrogated collateral growth in OZR, we employed VEGF gene therapy (VEGF-transduced, strained-matched, cultured vascular smooth muscle cells [cVSMCs], delivered intracoronary).VEGF therapy modestly but not significantly increased the CZ/NZ ratio afterRI (0.16 ± 0.05 vs 0.33 ± 0.06). To facilitate VEGF signaling, we reduced oxidative stress by transducing cVSMCs with both ecSOD and VEGF. This increasedthe CZ/NZ flow ratio after RI to 0.52 ± 0.04 (p < 0.05 vs. OZR[(0.19 ± 0.04]) indicating partial restoration of collateral growth. Our results demonstrate that coronary collateral growth is impaired in a model of the metabolic syndrome and that growth factor gene therapy with VEGF is made far more effective when it is coupled to an intervention that reduces oxidative stress.

Original languageEnglish (US)
Pages (from-to)217-223
Number of pages7
JournalBasic Research in Cardiology
Volume102
Issue number3
DOIs
StatePublished - May 1 2007
Externally publishedYes

Fingerprint

Zucker Rats
Intercellular Signaling Peptides and Proteins
Growth
Oxidative Stress
Vascular Smooth Muscle
Genetic Therapy
Smooth Muscle Myocytes
Microspheres
Coronary Artery Disease
Ischemia
Obesity

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Restoration of coronary collateral growth in the Zucker obese rat : Impact of VEGF and ecSOD. / Hattan, Naoichiro; Chilian, William M.; Park, Frank; Rocic, Petra.

In: Basic Research in Cardiology, Vol. 102, No. 3, 01.05.2007, p. 217-223.

Research output: Contribution to journalArticle

Hattan, Naoichiro ; Chilian, William M. ; Park, Frank ; Rocic, Petra. / Restoration of coronary collateral growth in the Zucker obese rat : Impact of VEGF and ecSOD. In: Basic Research in Cardiology. 2007 ; Vol. 102, No. 3. pp. 217-223.
@article{b7d6a1997fee46e8978890b46c6a07aa,
title = "Restoration of coronary collateral growth in the Zucker obese rat: Impact of VEGF and ecSOD",
abstract = "The metabolic syndrome (MS), a condition characterized byseveral risk factors for coronary artery disease, including obesity, is associatedwith endothelial dysfunction and oxidative stress. Because proper endothelial function is essential for signaling of certain growth factors (vascularendothelial growth factor, VEGF) we hypothesized that coronary collateral growth (CCG) is impaired in a model of the MS. To test this hypothesis,we stimulated coronary collateral growth in pre-diabetic Zuckerobese fatty rats (OZR) and lean littermates (LZR) by using episodic, repetitive ischemia (RI: 40 s left anterior descending arterial occlusion, 24/d for 14d). Myocardial blood flow (MBF, radioactive microspheres) was measured inthe normal (NZ) and collateral-dependent (ischemic) zones (CZ); CCG was assessed as a ratio of CZ/NZ flow (unity represents complete restoration ofCZ flow). In LZR, CZ/NZ ratio increased from 0.18 ± 0.03 to 0.81± 0.07 afterRI (P < 0.05). In contrast, in OZR rats CZ/NZ did not increase after RI(0.15 ± 0.04 vs 0.18 ± 0.04). To rectify abrogated collateral growth in OZR, we employed VEGF gene therapy (VEGF-transduced, strained-matched, cultured vascular smooth muscle cells [cVSMCs], delivered intracoronary).VEGF therapy modestly but not significantly increased the CZ/NZ ratio afterRI (0.16 ± 0.05 vs 0.33 ± 0.06). To facilitate VEGF signaling, we reduced oxidative stress by transducing cVSMCs with both ecSOD and VEGF. This increasedthe CZ/NZ flow ratio after RI to 0.52 ± 0.04 (p < 0.05 vs. OZR[(0.19 ± 0.04]) indicating partial restoration of collateral growth. Our results demonstrate that coronary collateral growth is impaired in a model of the metabolic syndrome and that growth factor gene therapy with VEGF is made far more effective when it is coupled to an intervention that reduces oxidative stress.",
author = "Naoichiro Hattan and Chilian, {William M.} and Frank Park and Petra Rocic",
year = "2007",
month = "5",
day = "1",
doi = "10.1007/s00395-007-0646-3",
language = "English (US)",
volume = "102",
pages = "217--223",
journal = "Basic Research in Cardiology",
issn = "0300-8428",
publisher = "D. Steinkopff-Verlag",
number = "3",

}

TY - JOUR

T1 - Restoration of coronary collateral growth in the Zucker obese rat

T2 - Impact of VEGF and ecSOD

AU - Hattan, Naoichiro

AU - Chilian, William M.

AU - Park, Frank

AU - Rocic, Petra

PY - 2007/5/1

Y1 - 2007/5/1

N2 - The metabolic syndrome (MS), a condition characterized byseveral risk factors for coronary artery disease, including obesity, is associatedwith endothelial dysfunction and oxidative stress. Because proper endothelial function is essential for signaling of certain growth factors (vascularendothelial growth factor, VEGF) we hypothesized that coronary collateral growth (CCG) is impaired in a model of the MS. To test this hypothesis,we stimulated coronary collateral growth in pre-diabetic Zuckerobese fatty rats (OZR) and lean littermates (LZR) by using episodic, repetitive ischemia (RI: 40 s left anterior descending arterial occlusion, 24/d for 14d). Myocardial blood flow (MBF, radioactive microspheres) was measured inthe normal (NZ) and collateral-dependent (ischemic) zones (CZ); CCG was assessed as a ratio of CZ/NZ flow (unity represents complete restoration ofCZ flow). In LZR, CZ/NZ ratio increased from 0.18 ± 0.03 to 0.81± 0.07 afterRI (P < 0.05). In contrast, in OZR rats CZ/NZ did not increase after RI(0.15 ± 0.04 vs 0.18 ± 0.04). To rectify abrogated collateral growth in OZR, we employed VEGF gene therapy (VEGF-transduced, strained-matched, cultured vascular smooth muscle cells [cVSMCs], delivered intracoronary).VEGF therapy modestly but not significantly increased the CZ/NZ ratio afterRI (0.16 ± 0.05 vs 0.33 ± 0.06). To facilitate VEGF signaling, we reduced oxidative stress by transducing cVSMCs with both ecSOD and VEGF. This increasedthe CZ/NZ flow ratio after RI to 0.52 ± 0.04 (p < 0.05 vs. OZR[(0.19 ± 0.04]) indicating partial restoration of collateral growth. Our results demonstrate that coronary collateral growth is impaired in a model of the metabolic syndrome and that growth factor gene therapy with VEGF is made far more effective when it is coupled to an intervention that reduces oxidative stress.

AB - The metabolic syndrome (MS), a condition characterized byseveral risk factors for coronary artery disease, including obesity, is associatedwith endothelial dysfunction and oxidative stress. Because proper endothelial function is essential for signaling of certain growth factors (vascularendothelial growth factor, VEGF) we hypothesized that coronary collateral growth (CCG) is impaired in a model of the MS. To test this hypothesis,we stimulated coronary collateral growth in pre-diabetic Zuckerobese fatty rats (OZR) and lean littermates (LZR) by using episodic, repetitive ischemia (RI: 40 s left anterior descending arterial occlusion, 24/d for 14d). Myocardial blood flow (MBF, radioactive microspheres) was measured inthe normal (NZ) and collateral-dependent (ischemic) zones (CZ); CCG was assessed as a ratio of CZ/NZ flow (unity represents complete restoration ofCZ flow). In LZR, CZ/NZ ratio increased from 0.18 ± 0.03 to 0.81± 0.07 afterRI (P < 0.05). In contrast, in OZR rats CZ/NZ did not increase after RI(0.15 ± 0.04 vs 0.18 ± 0.04). To rectify abrogated collateral growth in OZR, we employed VEGF gene therapy (VEGF-transduced, strained-matched, cultured vascular smooth muscle cells [cVSMCs], delivered intracoronary).VEGF therapy modestly but not significantly increased the CZ/NZ ratio afterRI (0.16 ± 0.05 vs 0.33 ± 0.06). To facilitate VEGF signaling, we reduced oxidative stress by transducing cVSMCs with both ecSOD and VEGF. This increasedthe CZ/NZ flow ratio after RI to 0.52 ± 0.04 (p < 0.05 vs. OZR[(0.19 ± 0.04]) indicating partial restoration of collateral growth. Our results demonstrate that coronary collateral growth is impaired in a model of the metabolic syndrome and that growth factor gene therapy with VEGF is made far more effective when it is coupled to an intervention that reduces oxidative stress.

UR - http://www.scopus.com/inward/record.url?scp=34147134616&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34147134616&partnerID=8YFLogxK

U2 - 10.1007/s00395-007-0646-3

DO - 10.1007/s00395-007-0646-3

M3 - Article

VL - 102

SP - 217

EP - 223

JO - Basic Research in Cardiology

JF - Basic Research in Cardiology

SN - 0300-8428

IS - 3

ER -