Left Ventricular Dysfunction with Reduced Functional Cardiac Reserve in Diabetic and Non-diabetic LDL-receptor Deficient Apolipoprotein B100-only Mice

Overview

Journal Cardiovasc Diabetol

Publisher Biomed Central

Specialties Cardiology & Vascular Diseases
Endocrinology

Date 2011 Jul 2

PMID 21718508

Citations 10

Authors

Suvi E Heinonen

Mari Merentie

Marja Hedman

Petri I Makinen

Elina Loponen

Ivana Kholova

Fatima Bosch

Markku Laakso

Seppo Yla-Herttuala

Affiliations

Soon will be listed here.

Abstract

Background: Lack of suitable mouse models has hindered the studying of diabetic macrovascular complications. We examined the effects of type 2 diabetes on coronary artery disease and cardiac function in hypercholesterolemic low-density lipoprotein receptor-deficient apolipoprotein B100-only mice (LDLR-/-ApoB100/100).

Methods And Results: 18-month-old LDLR-/-ApoB100/100 (n = 12), diabetic LDLR-/-ApoB100/100 mice overexpressing insulin-like growth factor-II (IGF-II) in pancreatic beta cells (IGF-II/LDLR-/-ApoB100/100, n = 14) and age-matched C57Bl/6 mice (n = 15) were studied after three months of high-fat Western diet. Compared to LDLR-/-ApoB100/100 mice, diabetic IGF-II/LDLR-/-ApoB100/100 mice demonstrated more calcified atherosclerotic lesions in aorta. However, compensatory vascular enlargement was similar in both diabetic and non-diabetic mice with equal atherosclerosis (cross-sectional lesion area ~60%) and consequently the lumen area was preserved. In coronary arteries, both hypercholesterolemic models showed significant stenosis (~80%) despite positive remodeling. Echocardiography revealed severe left ventricular systolic dysfunction and anteroapical akinesia in both LDLR-/-ApoB100/100 and IGF-II/LDLR-/-ApoB100/100 mice. Myocardial scarring was not detected, cardiac reserve after dobutamine challenge was preserved and ultrasructural changes revealed ischemic yet viable myocardium, which together with coronary artery stenosis and slightly impaired myocardial perfusion suggest myocardial hibernation resulting from chronic hypoperfusion.

Conclusions: LDLR-/-ApoB100/100 mice develop significant coronary atherosclerosis, severe left ventricular dysfunction with preserved but diminished cardiac reserve and signs of chronic myocardial hibernation. However, the cardiac outcome is not worsened by type 2 diabetes, despite more advanced aortic atherosclerosis in diabetic animals.

Citing Articles

Increased Calcific Aortic Valve Disease in response to a diabetogenic, procalcific diet in the LDLrApoB mouse model.

Scatena M, Jackson M, Speer M, Leaf E, Wallingford M, Giachelli C Cardiovasc Pathol. 2018; 34:28-37.

PMID: 29539583 PMC: 5940574. DOI: 10.1016/j.carpath.2018.02.002.

In vivo inhibition of nuclear factor of activated T-cells leads to atherosclerotic plaque regression in IGF-II/LDLRApoB mice.

Blanco F, Heinonen S, Gurzeler E, Berglund L, Dutius Andersson A, Kotova O Diab Vasc Dis Res. 2018; 15(4):302-313.

PMID: 29499628 PMC: 6039864. DOI: 10.1177/1479164118759220.

Arterial Calcification in Diabetes Mellitus: Preclinical Models and Translational Implications.

Stabley J, Towler D Arterioscler Thromb Vasc Biol. 2017; 37(2):205-217.

PMID: 28062508 PMC: 5480317. DOI: 10.1161/ATVBAHA.116.306258.

Type 2 diabetes enhances arterial uptake of choline in atherosclerotic mice: an imaging study with positron emission tomography tracer ¹⁸F-fluoromethylcholine.

Hellberg S, Silvola J, Kiugel M, Liljenback H, Metsala O, Viljanen T Cardiovasc Diabetol. 2016; 15:26.

PMID: 26852231 PMC: 4744438. DOI: 10.1186/s12933-016-0340-6.

Animal models of diabetic macrovascular complications: key players in the development of new therapeutic approaches.

Heinonen S, Genove G, Bengtsson E, Hubschle T, Akesson L, Hiss K J Diabetes Res. 2015; 2015:404085.

PMID: 25785279 PMC: 4345079. DOI: 10.1155/2015/404085.

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