Thyroid hormone, Although most victims survive the 735,000 heart attacks that occur annually in the U.S., their heart tissue is often irreparably damaged unlike many other cells in the body, once injure, heart cells cannot regenerate. According to a new UC San Francisco study.
The issue may date back to our earliest mammalian ancestors; which may have lost the ability to regenerate heart tissue in exchange for endothermy or as it’s know colloquially, “warm bloodedness” a Faustian evolutionary bargain that usher in the age of mammals; but left modern humans vulnerable to irreparable tissue damage after heart attack.
Early mammals were small, rodent like creatures that emerge in a world dominate by cold-blooded animals. Rather than compete directly, early mammals evolved a novel strategy that enabled them to occupy new niches: endothermy. While cold-blooded animals, unable to regulate their own body temperature, were hostage to ever changing weather conditions and relegated to temperate climates, warm blood mammals were able to spread to colder climes and to thrive nocturnally.
The thyroid gland produces a pair of well-studied hormones; so that are know to regulate body temperature, metabolic rate and normal heart function. Because of their critical role in promoting heat generation to maintain body temperature; so these hormones have posited to be the driving force behind the evolutionary transition from cold- to warm-bloodedness.
But Huang’s study reveal that these hormones are also responsible for shutting off cardiac cell division, thus preventing heart tissue from repairing itself after an injury. This discovery represents the first demonstrate connection between thyroid hormones, cardiac development and repair, and the evolution of endothermy.
Huang’s team took a multi-species approach, comparing heart cell “ploidy” the number of copies of each chromosome pair in a cell across 41 different vertebrate species. Ploidy is closely link to a cell’s ability to divide and replicate. Virtually all actively dividing animal cells are diploid, containing only one pair of each chromosome, a copy inherit from mothers and another from fathers. By contrast, polyploid cells contain multiple copies of each pair and generally can’t divide.
The cardiac injury
This comparative approach revealed a clear connection between ploidy and body temperature. Cold blood animals fish, amphibians and reptiles have heart cells that were largely diploid and respond to cardiac injury by ramping up cell division. Warm blood mammals had heart cells that were overwhelmingly polyploid, and lab experiments confirm that these cells rarely divide in response to cardiac damage.
Experiments show that these events were more than mere coincidence. When the researchers inject newborn mice with a drug that block thyroid hormone receptors; also inspect their hearts two weeks later; so they find four times as many dividing diploid heart muscle cells than mice that receive no drug. Similar results were observe when they administer a different drug that impeded the production of thyroid hormones.
In stark contrast to mice and other mammals, adult zebrafish have relatively low levels of circulating thyroid hormone. This led Huang to wonder whether increasing the levels of thyroid hormone be shut off the self-repair machinery that makes zebrafish hearts uncommonly resilient.
Our results demonstrate an evolutionarily conserved function for thyroid hormone; so in regulating heart cell proliferation and suggest that loss of regenerative potential; which was a trade-off that allow mammals to become warm-blooded,” Huang said. “For early mammals, endothermy was more advantageous than retention of regenerative potential. But now, with medical improvements allowing us to live much longer; so this loss of cardiac regeneration becomes more problematic and is a fundamental cause of heart disease.