Monocyte-Derived Macrophages Aggravate Cardiac Dysfunction After Ischemic Stroke in Mice

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).