MicroRNAs in Preeclampsia.

Preeclampsia (PE) continues to represent a worldwide problem and challenge for both clinicians and laboratory-based doctors. Despite many efforts, the knowledge acquired regarding its pathogenesis and pathophysiology does not allow us to treat it efficiently. It is not possible to arrest its progressive nature, and the available therapies are limited to symptomatic treatment. Furthermore, both the diagnosis and prognosis are frequently uncertain, whilst the ability to predict its occurrence is very limited. MicroRNAs are small non-coding RNAs discovered two decades ago, and present great interest given their ability to regulate almost every aspect of the cell function. A lot of evidence regarding the role of miRNAs in pre-eclampsia has been accumulated in the last 10 years. Differentially expressed miRNAs are characteristic of both mild and severe PE. In many cases they target signaling pathway-related genes that result in altered processes which are directly involved in PE. Immune system, angiogenesis and trophoblast proliferation and invasion, all fundamental aspects of placentation, are controlled in various degrees by miRNAs which are up- or downregulated. Finally, miRNAs represent a potential therapeutic target and a diagnostic tool.

Optimizing the Management of Uncontrolled Hypertension: What do Triple Fixed-Dose Drug Combinations Add?

Fixed-dose triple drug combinations represent one of the latest innovations of pharmacotherapy for hypertension (HT). They combine a traditional renin-angiotensin system blocker, a diuretic and a calcium channel blocker. The main benefit is the simplification of treatment regimen because 3 different agents are combined at different doses in a single pill. Improving adherence to treatment partly explains why this kind of combination may effectively reduce blood pressure (BP). BP lowering by a single- pill triple-drug combination can be approximately predicted, by using appropriate formulas described in previous meta-analysis of randomized trials. Thus, clinicians may select the appropriate dose for each of the combined drugs. Selection of different types of fixed-dose triple-drug combinations relies upon clinical experience, commercial availability and evidence from clinical trials and metaanalyses for each agent alone. However, triple fixed-dose drug combinations should be reserved only for patients with uncontrolled BP with 2 agents, poor adherence in complex therapeutic regimens or on inappropriate free-drug combinations. Also, triple therapy may help overcome clinical inertia by prescribing more potent antihypertensive formulations in one pill. In contrast, this type of multiple-drug fixed-dose combination might be less safe in very old and frail patients, as well as in those with chronic kidney disease. Although new combinations may help overcome the clinical inertia of achieving individualized BP targets, doctors should also pay attention reinforcement of lifestyle changes.

Angiotensin receptor neprilysin inhibitor LCZ696: a novel targeted therapy for arterial hypertension?

The need for novel antihypertensive therapies represents a continuous challenge. LCZ696 is a first-in-class angiotensin receptor neprilysin inhibitor that has been shown to enhance endogenous natriuretic peptide (NP) actions on neurohormonal activation. This effect seems to be additive to that of the renin-angiotensin-aldosterone system (RAAS) suppression, as impressively suggested in the PARADIGM HF study. LCZ696 has been shown to be effective in reducing blood pressure in several small studies; however, its effectiveness and safety remain to be proved in larger studies. This review summarizes the role of RAAS and NP system in the pathophysiology of hypertension and reviews the current data on the antihypertensive effects of LCZ696.