title: Coronary capillary network remodeling and hypofibrinolysis in aged obese diabetic rats: implications for increased myocardial vulnerability to ischemia.
abstract: Despite the known abnormalities of cardiac function in patients with overt non-insulin dependent diabetes mellitus (NIDDM) the temporal changes of coronary capillary network remodeling leading to potential microcirculatory dysfunction have not been elucidated. To this end, left ventricular subendocardial capillary network of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, characterized by hypertension, obesity, hyperglycemia, hyperinsulinemia and mild NIDDM, and control Long-Evans Tokushima (LETO) rats were investigated. Total capillary density in OLETF was significantly higher than that in LETO at 20 weeks, suggesting compensatory improvement of O2 transport at early stages of NIDDM. The increase in capillary density in OLETF was lost at 40 and 60 weeks due to the decreases of intermediate capillary portions and venular capillary portions. Although capillary domain area (area innervated by single capillary) in OLETF was lower than that in LETO at 20 weeks, the values were similar between OLETF and LETO at 40 and 60 weeks, suggesting that adaptive improvement in the capacity for 02 transport with a high perfusion was lost in late stages of NIDDM. Activity of plasma plasminogen activator inhibitor-1 (PAI-1), the major physiologic inhibitor of proteo(fibrino)lysis, in OLETF was higher than that in LETO at 40 and 60 weeks, suggesting that increase of PAI-1 may downregulate compensatory adaptive capillary network remodeling by inhibiting proteolysis and angiogenesis in the cardiac interstitium. Loss of adaptive myocardial microcirculation may therefore contribute to increased vulnerability in ischemic injury and to cardiac dysfunction in NIDDM.
authors.affiliation: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Kitaku, Sapporo, Japan.
authors.forename: Taeko
authors.initials: T
authors.lastname: Sugawara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujii
authors.forename: A K M Tarikuz
authors.initials: AK
authors.lastname: Zaman
authors.forename: Daisuke
authors.initials: D
authors.lastname: Goto
authors.forename: Tomoo
authors.initials: T
authors.lastname: Furumoto
authors.forename: Shogo
authors.initials: S
authors.lastname: Imagawa
authors.forename: Jie
authors.initials: J
authors.lastname: Dong
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sakuma
authors.forename: Subrina
authors.initials: S
authors.lastname: Jesmin
authors.forename: Hiroko
authors.initials: H
authors.lastname: Togashi
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoshioka
authors.forename: Tomiyasu
authors.initials: T
authors.lastname: Koyama
authors.forename: Akira
authors.initials: A
authors.lastname: Kitabatake
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002196:Capillaries / Q000502:physiology*; D003326:Coronary Circulation / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D003929:Diabetic Neuropathies; D007328:Insulin / Q000097:blood; D008297:Male; D017202:Myocardial Ischemia; D009765:Obesity / Q000473:pathology; D010100:Oxygen / Q000378:metabolism; D010477:Perfusion; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D051381:Rats; D020334:Rats, Inbred OLETF; D020318:Rats, Long-Evans; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D010100:Oxygen