Abstract 16013: Impact of Mood Disorders on Atherosclerosis: An Experimental Model of Depression/Anxiety and Atherosclerosis
Introduction: Cardiovascular disease (CVD) and mood disorders remain the leading cause of mortality and hospitalization in industrialized countries. Co-morbidity between mood disorders and severity of cardiovascular disease is well known; however, the existence of a causal link is unclear.
Hypothesis: Mood disorders raise the risk of cardiovascular events by increasing atherosclerotic plaque instability and platelet aggregation.
Methods: ApoE–/– mice (n=28) were exposed to chronic social defeat stress while on Western diet for 6 months. ApoE–/– (n=8) not exposed to social defeat served as controls (C). Defeated animals were categorized as either susceptible (S, n=13; depression/anxiety) or resilient (R, n=7; anxiety) phenotypes based on social interaction test. Platelet reactivity to Serotonin:ADP (5-HT:ADP;10μM:6.5μM) or Serotonin:epinephrine (5HT:EPI;10μM: 5μM) was tested acutely after social defeat and at 6 months, using Multiplate Analyzer . Micro-SPECT Annexin A5 served to image plaque’s apoptosis. Uptake of 99mTc-Annexin A5 in plaques was quantified by γ-scintillation counting. Aortas and aortic roots were harvested and stained for MOMA-2 (Macrophages, Mac), α-actin (vascular smooth muscle cells, VSMCs), TUNEL and active caspase-3.
Results: Cellular composition analysis showed increased Mac density in R vs. S and C (Figure 1 A, D). VSMC density and VSMC/Mac ratio were lower in R and S vs. C (Figure 1 B-D). Higher uptake of Annexin A5 (Figure 1 E, F) and active caspase-3 staining (Figure 1 G, H) were observed in R vs. S. Increased platelet reactivity to 5HT:EPI was observed acutely after social defeat in R vs. S and C (Figure 1 I).
Conclusions: Our data demonstrate increased features of plaque vulnerability and platelet reactivity in resilient vs. susceptible mice in an experimental model of mood disorders and atherosclerosis. These data suggest a major role of stress on the progression and thrombotic complications of atherosclerosis.
- © 2013 by American Heart Association, Inc.