Cardiac Resident Macrophages Prevent Fibrosis and Stimulate Angiogenesis.

Area of Science:

• Cardiovascular Biology
• Immunology
• Cardiac Hypertrophy

Background:

• Cardiac pressure overload initially causes compensatory hypertrophy, but sustained stress leads to heart failure.
• Recruited macrophages influence the transition from compensated to decompensated hypertrophy.
• The role of cardiac resident immune cells in early hypertrophy remains unclear.

Purpose of the Study:

• To investigate the role of cardiac immune cells in the early stages of hypertrophy following pressure overload.
• To understand the specific contribution of cardiac resident macrophages to the initial hypertrophic response.

Main Methods:

• Flow cytometry and Cite-Seq single-cell RNA sequencing were used to analyze cardiac immune cells post-transverse aortic constriction (TAC).
• Macrophage colony-stimulating factor 1 receptor (CD115) blocking antibodies were employed to selectively deplete resident macrophages.
• CCR2 knockout mice were used to assess the role of monocyte-derived macrophages in fibrosis.

Main Results:

• TAC induced a significant increase in cardiac macrophages within one week.
• Selective depletion of resident macrophages resulted in enhanced cardiac fibrosis and impaired angiogenesis.
• Aggravated fibrosis was linked to the recruitment of monocyte-derived macrophages.
• Early depletion of resident macrophages led to depressed cardiac function and increased fibrosis at 6 weeks post-TAC.

Conclusions:

• Cardiac resident macrophages are a distinct immune cell population crucial for early cardiac adaptation to pressure overload.
• These cells play vital roles in promoting angiogenesis and mitigating fibrosis.
• Dysfunction or depletion of resident macrophages exacerbates adverse cardiac remodeling and dysfunction.