Coronary arterioles in type 2 diabetic (db/db) mice undergo a distinct pattern of remodeling associated with decreased vessel stiffness

Katz, Paige S.; Trask, Aaron J.; Souza‐Smith, Flavia M.; Hutchinson, Kirk R.; Galantowicz, Maarten L.; Lord, Kevin; Stewart, James A.; Cismowski, Mary J.; Varner, Kurt J.; Lucchesi, Pamela A.

doi:10.1007/s00395-011-0201-0

Cited by 65 publications

(104 citation statements)

References 56 publications

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“…19 A previous study has shown that inward hypertrophic remodeling of coronary arterioles isolated from diabetic mice is associated with a decrease in vascular wall stiffness and reduced MBF and CFR. 20 In this study, our findings were consistent with the current literature and showed that FTY720 treatment lowered the expression of TGF-β and collagen, and reduced the extent of myocardial interstitial fibrosis in diabetic rat heart tissues.…”

Section: Discussionsupporting

confidence: 92%

Sphingosine-1-Phosphate Receptor Agonist, FTY720, Restores Coronary Flow Reserve in Diabetic Rats

Jin

et al. 2014

Circ J

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Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp vasomotor function. 12-14 By using PET with 13 N-ammonia, it is possible to measure myocardial perfusion in a non-invasive way and quantify myocardial blood flow (MBF) in a resting and pharmacologic stress phase with adenosine or dipyridamole (hyperemic response). 15 The use of 13 N-ammonia for quantification of MBF has been compromised by the non-linear relationship between tracer tissue retention and myocardial blood flow, and is suitable for the characterization of the status of coronary arteries and measuring the coronary perfusion reserve non-invasively.The purpose of the present study was to determine whether impaired coronary microvascular function in diabetic rats could be improved by the long-term administration of FTY720. We used the 13 NH3 MicroPET technique for detecting myocardial function in vivo to investigate the impact of CFR in the early stage of diabetes. oronary flow reserve (CFR) is a measure of the coronary vascular functionality and could be an important functional parameter to understand the pathophysiology of coronary microcirculation. 1 Impairment of CFR has been generally demonstrated in diabetic patients and animals with microvascular complications but without obvious obstructive coronary atherosclerosis. 2,3 Impaired CFR has been shown to confer great prognostic information for hard cardiovascular outcome, including all-cause mortality, cardiovascular death and non-fatal myocardial infarction. 4,5 FTY720, as a synthesized Sphingosine-1-phosphate (S1P) receptor agonist, can lower the inflammation reaction and promote lymph cell homing, 6,7 and has an important cardioprotective effect. Recently, it has been found that FTY720 has an important protect effect for diabetic microvessels and macrovessels. 8-11 To date, no study has found an improvement in CFR due to long-term FTY720 administration.Positron emission tomography (PET) is one of the few noninvasive methods available to quantitatively evaluate coronary There have been few studies investigating CFR in cases of relatively well-controlled therapy. The purpose of this study is to evaluate the effect of treatment with a Sphingosine-1-phosphate (S1P) receptor potent agonist, FTY720, on early diabetic rats in terms of CFR.

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Section: Discussionsupporting

confidence: 92%

Sphingosine-1-Phosphate Receptor Agonist, FTY720, Restores Coronary Flow Reserve in Diabetic Rats

Jin

et al. 2014

Circ J

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“…Our recent work suggests that coronary microvascular remodeling in type 2 diabetic db/db mice differed from aortic and mesenteric resistance vessels 1,12 . To understand molecular mechanisms that account for these differences, in vitro studies using low passage VSMCs are necessary.…”

Section: Representative Resultsmentioning

confidence: 92%

“…However, we have demonstrated vascular-bed specific remodeling in coronary, aortic, and mesenteric circulations of db/db mice 1 , suggesting the VSMCs in each vascular bed may be different. Therefore, it is necessary to isolate VSMCs from each vascular bed in order to better understand the pathological changes occurring in each set of VSMCs.…”

Section: Introductionmentioning

confidence: 74%

“…Our previous studies focused on the coronary microvessels (80-120 μm in diameter) 1,2 , however the main coronary arteries in mice are larger (>160 μm) 13 . In addition, this technique also isolates cells from the coronary venous circulation, not just the arterial circulation.…”

Section: Representative Resultsmentioning

confidence: 99%

“…We developed this technique to assess the molecular mechanisms of vascular remodeling in diabetes. We have previously reported inward hypertrophic remodeling in the septal coronary arterioles in the db/db mouse model of diabetes 1 . Due to the limited amount of tissue found in the murine septal coronaries, standard experimental techniques investigating protein changes (e.g.…”

Section: Introductionmentioning

confidence: 91%

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Isolation of Murine Coronary Vascular Smooth Muscle Cells

Husarek

Zhang

McCallinhart

et al. 2016

JoVE

Self Cite

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While the isolation and culture of vascular smooth muscle cells (VSMCs) from large vessels is well established, we sought to isolate and culture VSMCs from the coronary circulation. Hearts with intact aortic arches were removed and perfused via retrograde Langendorff with digestion solution containing 300 Units/ml of collagenase type II, 0.1 mg/ml soybean trypsin inhibitor and 1 M CaCl 2 . The perfusates were collected at 15 min intervals for 90 min, pelleted by centrifugation, resuspended in plating media, and plated on tissue culture dishes. VSMCs were characterized by presence of SM22α, α-SMA, and vimentin. One of the main advantages of using this technique is the ability to isolate VSMCs from the coronary circulation of mice. Although the small number of cells obtained can limit some of the applications for which the cells can be utilized, isolated coronary VSMCs can be used in a variety of well-established cell culture techniques and assays. Studies investigating VSMCs from genetically modified mice can provide further information about structure-function and signaling processes associated with vascular pathologies. Video LinkThe video component of this article can be found at

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