Renal Denervation and Atherosclerosis (page 758)
Sympathetic nervous system overactivity is associated with a variety of cardiovascular diseases. Sympathetic innervation to specific organs may be particularly relevant. For example, renal sympathetic activity may play an important role in hypertension by regulating renin–angiotensin–aldosterone system activity, as well as other humoral factors. These downstream factors may also affect other vascular disease processes, such as atherosclerosis, independent of hypertension. In this issue of Hypertension, Wang et al report the effects of renal denervation (RDN) in a normotensive, atherosclerosis-prone mouse model. Despite absence of effects on blood pressure or total cholesterol, mice receiving bilateral RDN developed less atherosclerosis compared with mice receiving a sham operation (Figure). Atherosclerotic lesions in RDN mice also appeared more stable with increased smooth muscle cell content. Protection from atherosclerosis in the RDN group was associated with reduction of systemic factors implicated in the progression of atherosclerosis, including aldosterone, monocyte chemoattractant protein-1, and a marker of oxidative stress, 8-isoprostane. Further studies will be necessary to identify the precise causal mechanism(s) responsible for the apparent beneficial effects of RDN on progression of atherosclerosis, so that this pathway might be targeted in subjects at high risk for vascular disease. Complications of atherosclerosis (or surrogate end points) should also be studied if future clinical RDN trials in humans are performed.
Preeclampsia Potentiates Future Vascular Injury (page 863)
Women who develop preeclampsia during pregnancy have an increased risk of cardiovascular disease later in life. Preeclampsia affects 5% of pregnancies, thereby exposing many women to increased cardiovascular risk for which there is no treatment aside from modification of traditional risk factors. The pervading explanation for this 2- to 4-fold increased cardiovascular risk is that preeclampsia identifies woman destined to develop cardiovascular disease. This is based on data revealing common risk factors for preeclampsia and cardiovascular disease. In this issue of Hypertension, Pruthi et al provide data supporting a novel emerging theory in which permanent vascular damage sustained during the preeclamptic episode contributes directly to cardiovascular disease pathogenesis. They demonstrate for the first time that mice exposed to experimental preeclampsia retain an enhanced response to vascular injury months after preeclampsia resolves. In their study, mice without preexisting cardiovascular risk factors were exposed to wire carotid injury 2 months after experimental preeclampsia. Preeclampsia-exposed mice developed increased vessel thickening and enhanced vascular cell proliferation and fibrosis after injury. Exploration of the mechanism for these persistent changes in the vasculature after preeclampsia has the potential to yield totally novel therapies to prevent this vascular damage during preeclampsia or to treat women after preeclampsia to avert the rapid progression to cardiovascular disease.
Sofalcone Upregulates Heme Oxygenase-1 and Decreases Soluble fms–Like Tyrosine Kinase 1 (page 855)
Preeclampsia complicates 3% to 8% of all pregnancies and is globally responsible for an estimated 60 000 maternal deaths annually and a far greater number of fetal losses. A therapeutic for preeclampsia could be a significant breakthrough, saving mothers and babies. Sadly, there is no such treatment. Solfacone is widely used as an antiulcer agent in Asia. In this issue of Hypertension, Onda et al report studies showing Solfacone has 3 different biological actions that raise the surprising possibility that it may be a treatment for preeclampsia. Preeclampsia is strongly associated with oxidative stress. The team reports Solfacone switches on a master transcription factor (Nrf2) that translocates to the nucleus and upregulates a raft of antioxidant genes. Secondly, the preeclamptic placenta produces elevated levels of soluble fms–like tyrosine kinase 1, which circulates widely, causing maternal endothelial dysfunction. Onda et al found Solfacone decreased soluble fms–like tyrosine kinase 1 secretion. Finally, circulating placental factors (including soluble fms–like tyrosine kinase 1) cause widespread endothelial dysfunction that leads to hypertension and multiple maternal organ injury. The team used several assays to show that Solfacone may protect blood vessels by decreasing endothelial dysfunction (Figure). Although there is little data on the safety of Solfacone in pregnancy, no links have been made with adverse pregnancy outcomes. Therefore, it is justifiable to proceed to clinical trials to treat women having severe preeclampsia with Solfacone where clinical options are limited.
- © 2015 American Heart Association, Inc.