TY - JOUR
T1 - Dynamic micro-and macrovascular remodeling in coronary circulation of obese Ossabaw pigs with metabolic syndrome
AU - Trask, Aaron J.
AU - Katz, Paige S.
AU - Kelly, Amy P.
AU - Galantowicz, Maarten L.
AU - Cismowski, Mary J.
AU - West, T. Aaron
AU - Neeb, Zachary P.
AU - Berwick, Zachary C.
AU - Goodwill, Adam G.
AU - Alloosh, Mouhamad
AU - Tune, Johnathan D.
AU - Sturek, Michael
AU - Lucchesi, Pamela A.
PY - 2012/10/1
Y1 - 2012/10/1
N2 - Previous studies from our laboratory showed that coronary arterioles from type 2 diabetic mice undergo inward hypertrophic remodeling and reduced stiffness. The aim of the current study was to determine if coronary resistance microvessels (CRMs) in Ossabaw swine with metabolic syndrome (MetS) undergo remodeling distinct from coronary conduit arteries. Male Ossabaw swine were fed normal (n 7, Lean) or hypercaloric high-fat (n 7, MetS) diets for 6 mo, and then CRMs were isolated and mounted on a pressure myograph. CRMs isolated from MetS swine exhibited decreased luminal diameters (126 ± 5 and 105 ± 9 μm in Lean and MetS, respectively, P < 0.05) with thicker walls (18 plusmn; 3 and 31 ± 3 μm in Lean and MetS, respectively, P < 0.05), which doubled the wall-to-lumen ratio (14 ± 2 and 30 ± 2 in Lean and MetS, respectively, P ± 0.01). Incremental modulus of elasticity (IME) and beta stiffness index (BSI) were reduced in CRMs isolated from MetS pigs (IME: 3.6 × 106 ± 0.7 × 106 and 1.1 × 10 6 ± 0.2 × 106 dyn/cm2 in Lean and MetS, respectively, P < 0.001; BSI: 10.3 plusmn; 0.4 and 7.3 ± 1.8 in Lean and MetS, respectively, P < 0.001). BSI in the left anterior descending coronary artery was augmented in pigs with MetS. Structural changes were associated with capillary rarefaction, decreased hyperemic-tobasal coronary flow velocity ratio, and augmented myogenic tone. MetS CRMs showed a reduced collagen-to-elastin ratio, while immunostaining for the receptor for advanced glycation end products was selectively increased in the left anterior descending coronary artery. These data suggest that MetS causes hypertrophic inward remodeling of CRMs and capillary rarefaction, which contribute to decreased coronary flow and myocardial ischemia. Moreover, our data demonstrate novel differential remodeling between coronary micro-and macrovessels in a clinically relevant model of MetS.
AB - Previous studies from our laboratory showed that coronary arterioles from type 2 diabetic mice undergo inward hypertrophic remodeling and reduced stiffness. The aim of the current study was to determine if coronary resistance microvessels (CRMs) in Ossabaw swine with metabolic syndrome (MetS) undergo remodeling distinct from coronary conduit arteries. Male Ossabaw swine were fed normal (n 7, Lean) or hypercaloric high-fat (n 7, MetS) diets for 6 mo, and then CRMs were isolated and mounted on a pressure myograph. CRMs isolated from MetS swine exhibited decreased luminal diameters (126 ± 5 and 105 ± 9 μm in Lean and MetS, respectively, P < 0.05) with thicker walls (18 plusmn; 3 and 31 ± 3 μm in Lean and MetS, respectively, P < 0.05), which doubled the wall-to-lumen ratio (14 ± 2 and 30 ± 2 in Lean and MetS, respectively, P ± 0.01). Incremental modulus of elasticity (IME) and beta stiffness index (BSI) were reduced in CRMs isolated from MetS pigs (IME: 3.6 × 106 ± 0.7 × 106 and 1.1 × 10 6 ± 0.2 × 106 dyn/cm2 in Lean and MetS, respectively, P < 0.001; BSI: 10.3 plusmn; 0.4 and 7.3 ± 1.8 in Lean and MetS, respectively, P < 0.001). BSI in the left anterior descending coronary artery was augmented in pigs with MetS. Structural changes were associated with capillary rarefaction, decreased hyperemic-tobasal coronary flow velocity ratio, and augmented myogenic tone. MetS CRMs showed a reduced collagen-to-elastin ratio, while immunostaining for the receptor for advanced glycation end products was selectively increased in the left anterior descending coronary artery. These data suggest that MetS causes hypertrophic inward remodeling of CRMs and capillary rarefaction, which contribute to decreased coronary flow and myocardial ischemia. Moreover, our data demonstrate novel differential remodeling between coronary micro-and macrovessels in a clinically relevant model of MetS.
UR - http://www.scopus.com/inward/record.url?scp=84866992456&partnerID=8YFLogxK
U2 - 10.1152/japplphysiol.00604.2012
DO - 10.1152/japplphysiol.00604.2012
M3 - Article
C2 - 22837170
AN - SCOPUS:84866992456
SN - 8750-7587
VL - 113
SP - 1128
EP - 1140
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
IS - 7
ER -