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Published on: December 17, 2019
Monocyte-Derived Macrophages Aggravate Cardiac Dysfunction After Ischemic Stroke in Mice
Hong-Bin Lin1, Pu Hong1, Meng-Yu Yin1
1Department of Anesthesiology, Zhujiang Hospital Southern Medical University Guangzhou Guangdong China.
Insights
Ischemic stroke triggers cardiac damage via the cerebral-cardiac syndrome (CCS). This study reveals that activated cardiac sympathetic nerves drive monocyte-derived macrophage infiltration, worsening cardiac dysfunction in CCS.
Area of Science:
- Cardiovascular Research
- Neuroscience
- Immunology
Background:
- Cerebral-cardiac syndrome (CCS) describes cardiac damage following ischemic stroke.
- Cardiac macrophages are implicated in CCS, but their specific roles and interactions with sympathetic nerves remain unclear.
Purpose of the Study:
- To investigate the role of macrophage subsets and sympathetic nerves in the pathogenesis of cerebral-cardiac syndrome (CCS).
Main Methods:
- Utilized a middle cerebral artery occlusion mouse model to induce ischemic stroke.
- Assessed cardiac function using ECG and echocardiography.
- Employed Smart-seq2 RNA sequencing, CCR2 antagonist, NLRP3-deficient mice, cardiac sympathetic nerve tracers, and sympathectomy to analyze macrophage subsets and nerve involvement.
Main Results:
- Ischemic stroke led to significant cardiac dysfunction and increased infiltration of proinflammatory monocyte-derived macrophages into the heart.
- Blocking macrophage infiltration with a CCR2 antagonist or using NLRP3-deficient mice improved cardiac function.
- Activated cardiac sympathetic nerves were found to promote monocyte-derived macrophage infiltration, exacerbating cardiac dysfunction.
Conclusions:
- The findings highlight a novel cardiac sympathetic nerve-monocyte-derived macrophage axis contributing to the pathophysiology of cerebral-cardiac syndrome (CCS).
Background:
Cardiac damage induced by ischemic stroke, such as arrhythmia, cardiac dysfunction, and even cardiac arrest, is referred to as cerebral-cardiac syndrome (CCS). Cardiac macrophages are reported to be closely associated with stroke-induced cardiac damage. However, the role of macrophage subsets in CCS is still unclear due to their heterogeneity. Sympathetic nerves play a significant role in regulating macrophages in cardiovascular disease. However, the role of macrophage subsets and sympathetic nerves in CCS is still unclear.
Methods And Results:
In this study, a middle cerebral artery occlusion mouse model was used to simulate ischemic stroke. ECG and echocardiography were used to assess cardiac function. We used Cx3cr1GFPCcr2RFP mice and NLRP3-deficient mice in combination with Smart-seq2 RNA sequencing to confirm the role of macrophage subsets in CCS. We demonstrated that ischemic stroke-induced cardiac damage is characterized by severe cardiac dysfunction and robust infiltration of monocyte-derived macrophages into the heart. Subsequently, we identified that cardiac monocyte-derived macrophages displayed a proinflammatory profile. We also observed that cardiac dysfunction was rescued in ischemic stroke mice by blocking macrophage infiltration using a CCR2 antagonist and NLRP3-deficient mice. In addition, a cardiac sympathetic nerve retrograde tracer and a sympathectomy method were used to explore the relationship between sympathetic nerves and cardiac macrophages. We found that cardiac sympathetic nerves are significantly activated after ischemic stroke, which contributes to the infiltration of monocyte-derived macrophages and subsequent cardiac dysfunction.
Conclusions:
Our findings suggest a potential pathogenesis of CCS involving the cardiac sympathetic nerve-monocyte-derived macrophage axis.
