Immune regulation of systemic hypertension, pulmonary arterial hypertension, and preeclampsia: shared disease mechanisms and translational opportunities

Abstract

Systemic hypertension, preeclampsia, and pulmonary arterial hypertension (PAH) are diseases of high blood pressure in the systemic or pulmonary circulation. Beyond the well-defined contribution of more traditional pathophysiological mechanisms, such as changes in the renin-angiotensin-aldosterone system, to the development of these hypertensive disorders, there is substantial clinical evidence supporting an important role for inflammation and immunity in the pathogenesis of each of these three conditions. Over the last decade, work in small animal models, bearing targeted deficiencies in specific cytokines or immune cell subsets, has begun to clarify the immune-mediated mechanisms that drive changes in vascular structure and tone in hypertensive disease. By summarizing the clinical and experimental evidence supporting a contribution of the immune system to systemic hypertension, preeclampsia, and PAH, the current review highlights the cellular and molecular pathways that are common to all three hypertensive disorders. These mechanisms are centered on an imbalance in CD4 helper T cell populations, defined by excessive Th17 responses and impaired T activity, as well as the excessive activation or impairment of additional immune cell types, including macrophages, dendritic cells, CD8 T cells, B cells, and natural killer cells. The identification of common immune mechanisms in systemic hypertension, preeclampsia, and PAH raises the possibility of new therapeutic strategies that target the immune component of hypertension across multiple disorders.

Prediction of preterm birth with and without preeclampsia using mid-pregnancy immune and growth-related molecular factors and maternal characteristics

“…Given the breadth of data demonstrating common pathophysiological underpinning across spontaneous and provider initiated subtypes of PTB including among those ± preeclampsia [ 23 – 28 ], it appears possible that a predictive test could be developed that covers a wider range of PTB phenotoypes. For example, all PTB subtypes ± preeclampsia have been shown to have strong links to markers of immune function (e.g., cytokines and chemokines) [ 23 – 26 ] and to angiogenic growth factors (e.g., vascular endothelial growth factor (VEGF)) [ 27 , 28 ].…”

Immune and Apoptosis Mechanisms Regulating Placental Development and Vascularization in Preeclampsia

“…One hypothesis is that over activation of immune cells stimulates trophoblast apoptosis in preeclampsia (Jafri and Ormiston, 2017). Indeed, during healthy pregnancies, the nonrecognition of trophoblasts by maternal immune cells reduces the activation of inflammation, and this will consequently decrease the lysis of the trophoblasts present in the decidua (Cornelius, 2018).…”

Immune‑related pathophysiological causes relevant to a subset of patients with preeclampsia (Review)

“…Among these, the immune system may lie upstream as one of the underlying mechanisms of reduced placental perfusion (19). An unbalanced regulation of immune responses may aggravate systemic inflammation, oxidative stress and endothelial dysfunction, which provides new insight into the role of immune pathway in disease initiation (13,14,47).…”