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Aortic‐Banding and Ovariectomy Independently Promote Coronary Artery Stiffness and Structural Remodeling
Author(s) -
Ouyang An,
Hiemstra Jessica,
Olver T. Dylan,
Edwards Jenna C.,
Ivey Jan R.,
Thorne Pamela K.,
Emter Craig A.,
Fleenor Bradley S.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.687.11
Subject(s) - elastin , medicine , myograph , cardiology , arterial stiffness , artery , endocrinology , coronary arteries , ejection fraction , extracellular matrix , heart failure , blood pressure , pathology , chemistry , biochemistry
Recent work by our laboratory has demonstrated coronary artery stiffening associated with structural remodeling in male aortic‐banded mini‐swine, a model of pressure‐overload heart failure exhibiting characteristics of human heart failure with preserved ejection fraction (HFpEF). The prevalence of HFpEF increases dramatically in women after menopause, and the interaction between the natural decrease in sex hormones with aging and hypertension on coronary artery stiffness is poorly understood. Thus, we hypothesized aortic banding in female mini‐swine will promote mechanical stiffness of coronary arteries, which will be worsened by the loss of female sex hormones following ovariectomy (OVX). Additionally, we hypothesized increased vascular stiffness would be associated with changes to arterial structural remodeling proteins, specifically increased collagen I deposition, decreased elastin, and increased advanced glycation end products (AGEs). Female Yucatan mini‐swine (8 months old) were divided into four groups: Intact (INT, n=7), intact‐aortic banded (AB INT, n=7), ovariectomy (OVX, n=6) and aortic banded with ovariectomy (AB OVX, n=7). After 24 weeks, arterial stiffness was assessed in the left circumflex (LCX) coronary artery by ex vivo mechanical testing using a multi‐wire Myograph system. Extracellular matrix components collagen I, elastin, and AGEs protein expressions were assessed in coronary cross‐sections by immunohistochemical staining. Mechanical testing of the LCX demonstrated an increase in the collagen elastic modulus (CEM) in AB INT and AB OVX groups compared to INT and OVX only groups (main effect of AB, P < 0.05), which was associated with greater arterial collagen expression (main effect of AB, P < 0.05). Compared with INT, the elastin elastic modulus (EEM) was reduced in AB INT, OVX and AB OVX groups (604±46 vs. 382±42, 371±43, 357 ±32 kPa, respectively, P < 0.05) that was also associated with reductions in coronary elastin expression (22±2 vs. 14±1, 14±1, 15±1 AU, respectively, P < 0.05). AGEs accumulation in the LCX was greater in AB INT, OVX and AB OVX groups compared with INT (20±2, 25±2, 21±3 vs. 13±1 AU, respectively, P < 0.05). In summary, these findings indicate aortic banding and ovariectomy promote coronary artery stiffness and structural remodeling by independent mechanisms in a translational female swine model of pressure overload HF with potential relevance to human HFpEF.