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Effect of Age and High Fat Diet on the Pro‐Atherogenic Response to Oscillatory Blood Flow
Author(s) -
Walker Ashley E,
Breevoort Sarah R,
Durrant Jessica R,
Machin Daniel R,
Dobson Parker S,
Nielson Elizabeth I,
Donato Anthony J,
Lesniewski Lisa A
Publication year - 2016
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.30.1_supplement.730.4
Subject(s) - blood flow , medicine , neointima , carotid arteries , ligation , tunica intima , artery , ultrasound , endocrinology , cardiology , anatomy , radiology , restenosis , stent
Atherogenesis is more likely to occur in arteries at locations of greater oscillations in blood flow, such as branch points and curvatures. However, it is unknown if advancing age or a high fat diet affect the pro‐atherogenic response to increased oscillatory blood flow. To induce greater oscillatory blood flow, we performed partial carotid ligation (PCL) of the left carotid artery of young normal chow fed (YNC, 6.4±0.3 mo, n=10), young high fat fed (YHF, 6.0±0.2 mo, n=11), old normal chow fed (ONC, 29.0±0.1 mo, n=7), and old high fat fed (OHF, 29.7±0.3 mo, n=11) male B6D2F1 mice. After PCL, blood flow of the ligated (left) and control (right) carotids was measured by ultrasound. The pro‐atherogenic response was assessed in histological sections of carotids collected 3‐weeks post‐PCL by measurement of intima media thickness (IMT) and neointima formation. Additionally, a subset of histological samples were evaluated by a pathologist (n=3–5/group). After PCL surgery, antegrade blood flow was ~10‐fold less (p<0.001), but retrograde blood flow was not different between the ligated and control carotids (p>0.05). This resulted in an oscillatory index that was ~20‐fold higher in the ligated compared to the control carotids (p<0.001). Oscillatory index was not different between age or diet groups (p>0.05). Histological evaluation identified hypertrophied smooth muscle cells and separation of the mural elastic laminae in ligated carotids from all groups. On average, IMT was ~2 fold greater in the ligated carotid compared to the control carotid (p<0.001). Although IMT of the ligated carotid was not different between YNC and ONC mice (p>0.05), it was 52% greater in YHF compared to YNC (p<0.05) and 38% greater in OHF compared to ONC (p<0.05). Neointima formation in the ligated carotid was variable within groups and was primarily composed of smooth muscle cells and macrophages. Neointima was present in 20% of YNC, 45% of YHF, 14% of ONC, and 33% of OHF ligated carotids, but no neointima was present in control carotids from any group. In the ligated carotids, the percent of area within the internal elastic lamina composed of neointima was greater in YHF vs. YNC (19.5±7.4% vs. 4.3±2.8%, p<0.05) as well as in OHF vs. ONC (11.0±5.3% vs. 0.4±0.4%, p<0.05). The majority of YHF and OHF ligated carotids had adventitial or perivascular inflammation, extending into the media and intima in the most severe cases. However, minimal inflammation was present in YNC and ONC ligated carotids. In conclusion, we find a high fat diet, but not older age, leads to an exacerbated pro‐atherogenic response to increased oscillatory blood flow, indicated by greater IMT, neointima formation and vascular inflammation. Support or Funding Information Supported by NIH AG046326, AG043952, AG040297, Department of Veterans Affairs 1I01BX002151