Cardiac fibroblasts in pressure overload hypertrophy: the enemy within?

Area of Science:

• Cardiovascular Biology
• Fibroblast Biology
• Cardiac Pathophysiology

Background:

• Cardiac fibroblasts are implicated in heart disease, but their roles are unclear due to a lack of specific markers.
• Identifying fibroblast origins is crucial for understanding their contribution to cardiac remodeling and disease progression.

Purpose of the Study:

• To investigate the origin and proliferation of cardiac fibroblasts in response to pressure overload.
• To identify novel sources of fibroblasts contributing to cardiac disease.

Main Methods:

• Utilized a collagen1a1-green fluorescent protein (GFP) reporter mouse model for fibroblast lineage tracing.
• Induced cardiac pressure overload via aortic banding in mice.
• Analyzed fibroblast proliferation and origin using histological and molecular techniques.

Main Results:

• Fibroblast accumulation after aortic banding predominantly resulted from the proliferation of resident fibroblasts.
• Identified both the epicardium and a previously unrecognized source, the endocardium, as origins of these proliferating fibroblasts.
• Demonstrated distinct contributions of epicardial and endocardial fibroblasts to cardiac remodeling.

Conclusions:

• Resident fibroblasts, originating from both epicardium and endocardium, are the primary source of fibroblast expansion during cardiac pressure overload.
• This study uncovers the endocardium as a significant, previously unrecognized source of cardiac fibroblasts.
• Further research into fibroblast origin and function can inform the development of targeted cardiac therapies.