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Activated complement directly modifies the performance of isolated heart muscle cells from guinea pig and rat
H J Berger1, A Taratuska, T W Smith
1Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Insights
The complement system
Area of Science:
- Cardiovascular Science
- Immunology
- Cell Biology
Background:
- The complement system, particularly the membrane attack complex (C5b-9), is linked to cardiovascular diseases like ischemia and atherosclerosis.
- C5b-9 deposition is observed in human heart tissue after ischemia and in infarcted areas.
- The functional impact of C5b-9 on myocardial cells remains unclear.
Purpose of the Study:
- To investigate the functional consequences of C5b-9 binding to cardiac myocytes.
- To determine if C5b-9 affects intracellular calcium levels and myocyte contractility.
Main Methods:
- Experiments were conducted on isolated adult guinea pig and rat cardiac myocytes.
- Human-derived C5b-9 complexes were applied to the myocytes.
- Changes in basal cytosolic calcium concentration and calcium transients were measured.
- Myocyte contractility was assessed.
Main Results:
- C5b-9 application led to a dose-dependent, transient increase in basal cytosolic calcium concentration.
- C5b-9 also augmented calcium transients, causing a temporary rise in contractility.
- These effects occurred without causing cell lysis.
Conclusions:
- C5b-9 can transiently enhance cardiac myocyte calcium levels and contractility.
- These C5b-9-induced changes may contribute to myocardial dysfunction in conditions like ischemia.
- Further in vivo studies are needed to confirm these effects in human hearts.
Abstract:
The complement system has been implicated in the pathogenesis of cardiovascular disorders including ischemia and atherosclerosis. Selective deposition of C5b-9, the membrane attack complex of complement, has been histochemically documented in human myocardium early after reperfusion of ischemic areas and in infarcted zones. However, functional sequelae of the C5b-9 complex binding to myocardial cells have not been identified. Insertion of C5b-9 complexes into the membrane of other cell types can generate transient changes in membrane permeability in the absence of cell lysis. We demonstrate in beating isolated adult guinea pig and rat cardiac myocytes that human derived C5b-9 can transiently augment in a dose-dependent manner both basal cytosolic calcium concentration and calcium transients, resulting in a temporary increase in contractility. If similar changes occur in human heart cells in vivo, they could significantly affect myocardial performance and contribute to functional abnormalities seen in ischemia and other pathological conditions associated with complement activation.