Unbiased plasma proteomics for novel diagnostic biomarkers in cardiovascular disease: identification of quiescin Q6 as a candidate biomarker of acutely decompensated heart failure

Aims Biochemical marker testing has improved the evaluation and management of patients with cardiovascular diseases over the past decade. Natriuretic peptides (NPs), used in clinical practice to assess cardiac dysfunction, exhibit many limitations, however. We used an unbiased proteomics approach for the discovery of novel diagnostic plasma biomarkers of heart failure (HF). Methods and results A proteomics pipeline adapted for very low-abundant plasma proteins was applied to clinical samples from patients admitted with acute decompensated HF (ADHF). Quiescin Q6 (QSOX1), a protein involved in the formation of disulfide bridges, emerged as the best performing marker for ADHF (with an area under the receiver operator characteristic curve of 0.86, 95% confidence interval: 0.79-0.92), and novel isoforms of NPs were also identified. Diagnostic performance of QSOX1 for ADHF was confirmed in 267 prospectively collected subjects of whom 76 had ADHF. Combining QSOX1 to B-type NP (BNP) significantly improved diagnostic accuracy for ADHF by particularly improving specificity. Using thoracic aortic constriction in rats, QSOX1 was specifically induced within both left atria and ventricles at the time of HF onset. Conclusion The novel biomarker QSOX1 accurately identifies ADHF, particularly when combined with BNP. Through both clinical and experimental studies we provide lines of evidence for a link between ADHF and cardiovascular production of QSOX1.     

Monocyte heterogeneity in cardiovascular disease

Only a few decades ago, students of the pathophysiology of cardiovascular disease paid little heed to the involvement of inflammation and immunity. Multiple lines of evidence now point to the participation of innate and adaptive immunity and inflammatory signaling in a variety of cardiovascular conditions. Hence, interest has burgeoned in this intersection. This review will focus on the contribution of innate immunity to both acute injury to the heart muscle itself, notably myocardial infarction, and to chronic inflammation in the artery wall, namely atherosclerosis, the cause of most myocardial infarctions. Our discussion of the operation of innate immunity in cardiovascular diseases will focus on functions of the mononuclear phagocytes, with special attention to emerging data regarding the participation of different functional subsets of these cells in cardiovascular pathophysiology.     

Effects of dietary inorganic nitrate on static and dynamic breath-holding in humans

Inorganic nitrate has been shown to reduce oxygen cost during exercise. Since the nitrate-nitrite-NO pathway is facilitated during hypoxia, we investigated the effects of dietary nitrate on oxygen consumption and cardiovascular responses during apnea. These variables were measured in two randomized, double-blind, placebo-controlled, crossover protocols at rest and ergometer exercise in competitive breath-hold divers. Subjects held their breath for predetermined times along with maximum effort apneas after two separate 3-day periods with supplementation of potassium nitrate/placebo.     

Making a Difference: Monocyte Heterogeneity in Cardiovascular Disease

Monocytes are frequently described as bone marrow-derived precursors of macrophages. Although many studies support this view, we now appreciate that monocytes neither develop exclusively in the bone marrow nor give rise to all macrophages and dendritic cells. In addition to differentiating to specific leukocyte populations, monocytes, as monocytes, are functionally and ontogenically heterogeneous. In this review we will focus on the development and activity of monocytes and their subsets in mice (Ly-6?C(high/low)) and humans (CD14(+/dim/-) CD16(+/-)) in the context of atherosclerosis and its complications.     

The rational of forehead lifting in patients with chronic facial paralysis

Background

The incidence of permanent facial sequels in patients with Bell’s palsy is about 30 % and results in impaired mimic expression of both midface and forehead in varying degrees. Even at rest, most patients experience an imbalance of their facial features. In this article, static correction of brow imbalance was evaluated in patients with sequels after unilateral facial palsy.

Methods

Thirty-one patients with sequels of Bell’s palsy underwent surgery with endoscopic forehead lift. Brow position was geometrically assessed pre- and postoperatively. The validated self-assessment instrument for quality of life [Short Form 36(SF-36)] was completed prior to and after surgery. The follow-up period was 12 months.

Results

A notable improvement in the position of the brows was demonstrated over time with lasting results. All patients experienced an improvement in facial symmetry and balance at rest. However, no significant difference could be shown using SF-36 pre- and postoperatively.

Conclusion

Endoscopic forehead lift combined or as an isolated procedure is a valuable instrument to correct sequels of Bell’s palsy. Level of Evidence: Level IV, therapeutic study.