Role of arterial impairment in preeclampsia: should the paradigm shift?

Abstract

Preeclampsia is a worldwide pregnancy complication with serious short and long-term maternal and neonatal consequences. Our understanding of preeclampsia pathophysiology has significantly evolved over the last decades with the recognition that impaired arterial function and structure may occur early in the course of pregnancy, preceding the clinic-humoral syndrome and driving long-term cardiovascular disease risk in the future of these patients. Although an early abnormal placentation may be the inciting event for a large proportion of cases, there is growing evidence that challenges the placental hypothesis in all affected women, since placental histopathology lesions thought to be characteristic are neither sensitive nor specific markers for the disorder. Recent hemodynamic investigations and studies on left ventricular function and structure in women with preeclampsia further challenge this universal paradigm and propose that placental dysfunction could be secondary to a maternal cardiovascular maladaptation to pregnancy in certain patients. Supporting this hypothesis, certain vascular features, which are characteristically enhanced in normal pregnancy allowing a healthy vascular adaptation are absent in preeclampsia and comparable to the non-pregnant population. However, arterial biomechanics in preeclampsia may only not cope with hemodynamic demands of pregnancy, but also impose additional detrimental loads to the maternal heart ("impaired left-ventricle-aorta coupling") and transmit pressure and flow disturbances into the fetoplacental circulation ("impaired large arteries-microcirculation coupling"). In this review, we analyze the major role of the arterial dysfunction in the cardiovascular maladaptation hypothesis of preeclampsia, shed light on its potential etiopathogenic link and discuss the complementary nature of the placental and cardiovascular theories.

Pathological AT1R-B2R Protein Aggregation and Preeclampsia

“…Emerging evidence suggests that impaired arterial function could in fact precede placental dysfunction [61]. Consequently, placental impairment would be secondary to cardiovascular dysfunction during the pathogenesis of preeclampsia [61,62]. In agreement with this concept, major risk factors of preeclampsia such as cardiovascular and metabolic diseases, cause damage to the vascular bed.…”

“…The unresolved question remains: What triggers placental dysfunction that ultimately causes preeclampsia hypertension? Emerging evidence suggests that impaired arterial function could in fact precede placental dysfunction [61]. Consequently, placental impairment would be secondary to cardiovascular dysfunction during the pathogenesis of preeclampsia [61,62].…”

Center-To-Periphery Arterial Stiffness Gradient Is Attenuated and/or Reversed in Pregnancy-Associated Hypertension

“…The most accepted theory proposes that an impaired placentation (i.e., shallow invasion of trophoblast of the spiral arteries) results in a dramatic rise in the resistance of the uterine-placental vasculature, which leads to a rapid development of a disproportionate rise in blood pressure (BP), inappropriate inflammatory response, generalized endothelial dysfunction, and multi-organ damage ("placental origin hypothesis") (4). However, this hypothesis was recently questioned, since placental histopathology lesions thought to be characteristic of this condition are neither sensitive nor specific markers for the disorder (5,6).…”

“…Recent evidence has revealed that PAH may develop in those women that are not able to develop an optimal cardiovascular adaptation to the naturally occurring hemodynamic loads of pregnancy ("cardiovascular origin hypothesis") (5,7). In this hemodynamic context (e.g., increased BP and arterial stiffness), excessive pulsatility in the central arteries may be preferentially transmitted to the placental microvasculature ("secondary placental dysfunction"), as well as to other vulnerable circulations.…”

Placental Ischemia Says “NO” to Proper NOS-Mediated Control of Vascular Tone and Blood Pressure in Preeclampsia

“…Placentation involves invasion of fetal-derived trophoblast cells that promote decidualization of the uterus with remodeling and widening of the maternal spiral arteries, as reviewed in [ 5 ]. Damage to the fetal-derived trophoblast cells that reside in the placenta and decidualized uterus is thought to mediate and propagate the maternal vascular dysfunction and hypertensive outcomes in PE, regardless of its gestational age of presentation [ 6 , 7 ]. Such damage can result from multiple factors, including malperfusion and resultant placental ischemia.…”