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Factors involved in capillary growth in the heart
O Hudlická1, M D Brown, H Walter
1Department of Physiology, University of Birmingham Medical School, UK.
Insights
Decreased heart rate, not increased blood flow, stimulates heart capillary growth. This bradycardia-induced growth may involve capillary wall stretch and growth factors like TGF-beta.
Area of Science:
- Cardiovascular Physiology
- Angiogenesis Research
Background:
- Capillary growth in the heart is linked to exercise, high altitude, and hormonal changes.
- Known stimuli include increased coronary blood flow and altered heart rate.
Purpose of the Study:
- To investigate if decreased heart rate alone stimulates cardiac capillary growth.
- To explore the mechanisms behind bradycardia-induced angiogenesis.
Main Methods:
- Long-term electrical bradycardial pacing in rabbits and pigs.
- Chronic administration of the bradycardic drug alinidine in rats.
- Analysis of capillary density (CD) and growth factor expression (ESAF, TGF-beta, FGF).
Main Results:
- Bradycardia induced capillary growth with minimal changes in coronary blood flow.
- Increased capillary wall tension and stretch were observed.
- Correlation found between capillary density and endothelial cell stimulating angiogenic factor (ESAF).
- TGF-beta mRNA levels increased in paced hearts.
Conclusions:
- Bradycardia is a direct stimulus for cardiac capillary growth.
- Mechanisms may involve mechanical stretch and growth factors like TGF-beta.
- ESAF is potentially involved in pacing-induced angiogenesis.
Abstract:
Growth of capillaries in the heart occurs under physiological circumstances during endurance exercise training, exposure to high altitude and/or cold, and changes in cardiac metabolism or heart rate elicited by modification of thyroid hormone levels. Capillary growth in all these conditions can be linked with increased coronary blood flow, decreased heart rate, or both. This paper brings evidence that, although increased blood flow due to long-term administration of coronary vasodilators results in capillary growth, a long-term decrease in heart rate induced by electrical bradycardial pacing in rabbits and pigs, or by chronic administration of a bradycardic drug, alinidine, in rats, stimulates capillary growth with little or no change in coronary blood flow. Decreased heart rate results in increased capillary wall tension, increased end-diastolic volume and increased force of contraction, and thus stretch of the capillary wall. This could lead to release of various growth factors possibly stored in the capillary basement membrane. Correlation was found between capillary density (CD) and the levels of low molecular endothelial cell stimulating angiogenic factor (ESAF) both in rabbit and pig hearts with CD increased by pacing. There was no relation between expression of mRNA for basic fibroblast growth factor and CD in sham-operated and paced rabbit hearts. In contrast, mRNA for TGF beta was increased in paced hearts, and the possible role of this factor in the regulation of capillary growth induced by bradycardia is discussed.