AUTHOR=An Lulu , Chopp Michael , Zacharek Alex , Shen Yi , Chen Zhili , Qian Yu , Li Wei , Landschoot-Ward Julie , Liu Zhongwu , Venkat Poornima 

TITLE=Cardiac Dysfunction in a Mouse Vascular Dementia Model of Bilateral Common Carotid Artery Stenosis

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 8 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.681572

DOI=10.3389/fcvm.2021.681572

ISSN=2297-055X

ABSTRACT=Background: Cardiac function is associated with cognitive function. Previously we found that stroke and traumatic brain injury evoke cardiac dysfunction in mice. In this study, we investigate whether Bilateral Common Carotid Artery Stenosis (BCAS), a model that induces vascular dementia (VaD) in mice, induces cardiac dysfunction.
Methods: Late-adult (6-8 month) C57BL/6J mice were subjected to sham surgery (n=6) or BCAS (n=8). BCAS was performed by applying microcoils (0.16mm internal diameter) around both common carotid arteries. Cerebral blood flow and cognitive function tests were performed 21-28 days post BCAS. Echocardiography was conducted at 29 days after BCAS. Mice were sacrificed 30 days after BCAS. Heart tissues were isolated for immunohistochemical evaluation and real time PCR assay. 
Results: Compared to sham mice, BCAS in mice significantly induced cerebral hypoperfusion and cognitive dysfunction, increased cardiac hypertrophy indicated by increased heart weight and the ratio of heart weight/body weight, and increased cardiac dysfunction, indicated by decreased Left Ventricular Ejection Fraction (LVEF), Left Ventricular Fractional Shortening (LVFS), increased interventricular septal thickness (IVST) and LV Mass. Cognitive deficits significantly correlated with cardiac deficits. BCAS mice also exhibited significantly increased cardiac fibrosis, increased oxidative stress as indicated by 4-Hydroxynonenal and NADPH oxidese-2, increased leukocytes and macrophages infiltration into heart, and increased cardiac Interleukin-6 and thrombin gene expression.
Conclusions: BCAS in mice without primary cardiac disease provokes cardiac dysfunction which, in part, may be mediated by increased inflammation and oxidative stress.