Macrophages Help Maintain a Healthy Heart Rhythm
Researchers have found that, in addition to playing an important role in clearing infectious agents and cellular debris, macrophages help conduct the electric signals that coordinate the heartbeat. The discovery that a new cell type is involved in orchestrating cardiac rhythm may lead to better understanding of normal heart function.
In a Cell study conducted in mice and human autopsy samples, a team led by investigators at Massachusetts General Hospital found that cardiac macrophages are especially abundant in the atrioventricular node that connects the atria to the ventricles and coordinates contraction timing for the upper and lower chambers.
Animal experiments also revealed that macrophages directly connect to heart muscle cells via pore-like gap junctions, and they depolarize in synchrony with their connected cardiomyocytes. The cardiac macrophages are not passive bystanders but influence conduction and change the electric properties of coupled cardiomyocytes. Until now, it has been widely accepted that atrioventricular conduction is mediated exclusively by specialized cardiomyocytes within the atrioventricular node.
Mice lacking connexin43 gap junctions exhibited an abnormal slowing of signal conduction through the atrioventricular node, and a complete depletion of tissue macrophages led to the development of atrioventricular block, a delay in conduction between the atria and ventricles that, in human patients, requires a pacemaker implantation.
Additional studies are needed to determine the mechanisms and extent to which macrophages maintain balance in the cardiac conduction system and how changes in their numbers or properties may contribute to heart rhythm abnormalities. Such research could point to the potential for targeted treatment of resident macrophages in a variety of cardiovascular diseases.
Prenatal Loss of a Father During War Predicts Reduced Life Span
Research on children who were conceived during the First World War supports the notion that intrauterine exposure to a major psychological maternal stress may affect an individual’s longevity.
For the Proceedings of the National Academy of Sciences study, investigators from France examined information from historical civil registers for 5671 children born between 1914 and 1916 who were granted the status of “pupille de la nation” (orphan of the nation). Drawing from a database of 1.4 million deceased soldiers, the team then identified war orphans, collected information on their fathers, and then paired each orphan with a nonorphan from the same birth register matched for date of birth, sex, and mother’s age at the infant’s birth. The final analysis included 2365 orphan/nonorphan pairs, with 27.7% of orphans being prenatal orphans and 72.3% being postnatal orphans.
When the researchers analyzed mortality between 31 and 99 years of age, they found that adult life span was different in prenatal orphans and their matched nonorphans, but there was no difference between postnatal orphans and matched nonorphans.
The average loss of adult life span of orphans who had lost their father before birth was 2.4 years, and there was a trend for a greater increase in adult mortality when the father’s death occurred during the third trimester of intrauterine life. A larger proportion of prenatal orphans (150 of 656) than matched nonorphans (107 of 656) died before 65 years of age, but no difference was found in remaining life span for those alive at the age of 65. Therefore, the 2.4-year difference in life expectancy reflected increased mortality between the ages of 31 and 65.
Of particular importance was the finding that adult life span was not reduced when the father’s death occurred after the infant’s birth. In addition, the decreased life span found in prenatal orphans could not be explained by degraded familial socioeconomic status because postnatal orphans faced comparable conditions in childhood and adolescence.
Additional research is needed to examine whether elevated maternal factors such as glucocorticoids may mediate the effects of stress during pregnancy on offspring longevity.
The findings of this study line up with a growing body of literature indicating that uterine exposures to factors such as malnutrition or toxins may trigger epigenetic changes in the chemical properties of DNA in the fetus. The causes of death in the individuals in the analysis are unknown but are likely related to cardiovascular health in some cases.
New Insights on How Vessels Relax After Vasoconstriction
Researchers investigating how blood vessel cells return to a relaxed state after contracting have found that depolarization—when signals trigger the influx of charged calcium ions into myocytes, leading to blood vessel narrowing—initiates a series of cellular events that cause one of the subunits of calcium-activated potassium channels, called β1, to travel from the cell interior to the surface. There, β1 subunits activate calcium-activated potassium channels, which attenuate calcium channel activity in arterial myocytes, limiting vasoconstriction.
The Science Signaling findings may have important clinical implications for a variety of cardiovascular conditions because abnormalities in β1 function have been associated with atherosclerosis, hypertension, and stroke. Furthermore, experimental evidence indicates that both the expression and function of the calcium-activated potassium channel change with aging.
The research team from the University of Tennessee Health Science Center also identified the specific proteins needed to bring β1 to the cell surface in both rat and human cells. The vasodilator nitric oxide mobilized the same β1 subunits but through a different signaling pathway.
Circulation is available at http://circ.ahajournals.org.
- © 2017 American Heart Association, Inc.