PREECLAMPSIA: Leptin, a cardiovascular cascade trigger

PREECLAMPSIA: Leptin, a cardiovascular cascade trigger

It is known that about 20 weeks after the start of a pregnancy, women with preeclampsia experience an increase in the production of leptin by the placenta, but the consequences have so far remained unknown. However, the team has just discovered that an increase in the hormone leptin – the hormone of satiety – in mid-pregnancy, associated with a reduction in appetite, produces a problematic dysfunction of blood vessels and a restriction of growth. of the baby, in case of preeclampsia, which puts the health of the mother and the baby at risk.

The increase in leptin, a marker of preeclampsia?

That’s the question posed by lead author Dr. Jessica Faulkner, a vascular physiologist at the Medical College of Georgia, and her team.

Leptin, mainly produced by fat cells, is also produced by the temporary organ, the placenta, which allows the mother to supply her developing baby with nutrients and oxygen. Leptin levels are known to increase steadily during a healthy pregnancy, but it is unclear what curve follows this increase. It has been hypothesized that leptin may be a natural nutrient scavenger during reproduction or a factor in the growth of new blood vessels and/or growth hormone stimulation.

Excess leptin and endothelial dysfunction: in preeclamptic patients, leptin levels increase more than they should: research reveals that this excessive increase in leptin leads to endothelial dysfunction in which blood vessels constrict, their ability to relax is impaired and the baby’s growth is limited. So when scientists inhibit the precursor to nitric oxide, a potent natural blood vessel dilator—similar to what happens in hypertension—it roughly mimics the effect of increased leptin in mid-pregnancy.

Leptin excess and vessel constriction: lincreased levels of leptin induce increased levels of blood vessel constrictor endothelin 1. Conversely, the suppression of the aldosterone receptor, in this case the mineralocorticoid receptors present on the surface of the cells lining the blood vessels, makes it possible to maintain normal endothelial function.

In question, a malformed placenta? The researchers hypothesize that in preeclamptic patients, at mid-pregnancy, fetal growth does not proceed as it should. The placenta compensates by increasing leptin production in an effort to restore more normal growth. But this seems to have the opposite effect, inducing endothelial dysfunction in particular, and harming the baby’s development.

If leptin had ever been associated with preeclampsia, the study is the first to show that when leptin rises, it worsens the symptoms of preeclampsia. Injecting pregnant mice with leptin in an attempt to mimic the flare that occurs in preeclampsia, in effect confirms the cascade of events described above, with the adrenal gland making more aldosterone, which increases the production of endothelin 1, also by the placenta.

This work thus provides a better understanding of the underlying mechanisms of increased blood pressure and other blood vessel dysfunctions during pregnancy, with new possible therapeutic targets to avoid devastating results for the mother and the child. baby. There are drugs like eplerenone, a blood pressure drug that binds to the mineralocorticoid receptor and effectively reduces the effect of higher levels of aldosterone.

The problems likely begin with the placenta and potentially inadequate blood flow to the temporary organ early in its development and the subsequent failure of development of the large blood vessels that become the passageway for nutrients and oxygen from mother to baby. .

While the incidence of preeclampsia is increasing – and has almost doubled in rich countries – with risk factors also on the rise, including obesity, chronic high blood pressure, type 1 or 2 diabetes , kidney disease, autoimmune disorders before pregnancy as well as the use of in vitro fertilization (IVF), targeting high levels of aldosterone and leptin is a new therapeutic option that should not be overlooked.

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