Kidney protective effects of baroreflex activation therapy in patients with resistant hypertension.

Baroreflex activation therapy (BAT) is approved for the treatment of resistant hypertension. In addition to blood pressure (BP) reduction, pilot studies suggested several organoprotective effects of BAT. Thirty-two patients with resistant hypertension were prospectively treated with BAT. Besides office BP and 24-hour ambulatory BP (ABP) measurements, detection of a urinary proteome-based classifier (CKD273), which has been shown to predict chronic kidney disease (CKD) progression, was carried out at baseline and after 6 months of BAT. Office BP significantly decreased from 170 ± 25/90 ± 18 to 149 ± 29/82 ± 18 mm Hg. Analysis of CKD273 score and eGFR with CKD-EPI equation at baseline revealed strong correlation (r = 0.568, P < 0.001). After 6 months of BAT, there was no significant change in CKD273 score (-0.061 [95% CI: -0.262 to 0.140], P = 0.601). However, by stratification of the data regarding ABP response, there was a statistically significant (P = 0.0113) reduction in the CKD273 score from a mean of 0.161 [95% CI: -0.093 to 0.414] to -0.346 [95% CI: -0.632 to -0.060] after BAT in patients with systolic ABP decrease of ≥5 mm Hg. These data emphasized potential nephroprotective effects of BAT in patients with sufficient BP response.

Clinical Proteomics for Precision Medicine: The Bladder Cancer Case.

Precision medicine can improve patient management by guiding therapeutic decision based on molecular characteristics. The concept has been extensively addressed through the application of -omics-based approaches. Proteomics attract high interest, as proteins reflect a "real-time" dynamic molecular phenotype. Focusing on proteomics applications for personalized medicine, a literature search was conducted to cover: a) disease prevention, b) monitoring/ prediction of treatment response, c) stratification to guide intervention, and d) identification of drug targets. The review indicates the potential of proteomics for personalized medicine by also highlighting multiple challenges to be addressed prior to actual implementation. In oncology, particularly bladder cancer, application of precision medicine appears especially promising. The high heterogeneity and recurrence rates together with the limited treatment options, suggest that earlier and more efficient intervention, continuous monitoring, and the development of alternative therapies could be accomplished by applying proteomics-guided personalized approaches. This notion is backed by studies presenting biomarkers that are of value in patient stratification and prognosis, and by recent studies demonstrating the identification of promising therapeutic targets. Herein, we aim to present an approach whereby combining the knowledge on biomarkers and therapeutic targets in bladder cancer could serve as basis towards proteomics-guided personalized patient management.

Impact of a 6-wk olive oil supplementation in healthy adults on urinary proteomic biomarkers of coronary artery disease, chronic kidney disease, and diabetes (types 1 and 2): a randomized, parallel, controlled, double-blind study.

BACKGROUND: Olive oil (OO) consumption is associated with cardiovascular disease prevention because of both its oleic acid and phenolic contents. The capacity of OO phenolics to protect against low-density lipoprotein (LDL) oxidation is the basis for a health claim by the European Food Safety Authority. Proteomic biomarkers enable an early, presymptomatic diagnosis of disease, which makes them important and effective, but understudied, tools for primary prevention. OBJECTIVE: We evaluated the impact of supplementation with OO, either low or high in phenolics, on urinary proteomic biomarkers of coronary artery disease (CAD), chronic kidney disease (CKD), and diabetes. DESIGN: Self-reported healthy participants (n = 69) were randomly allocated (stratified block random assignment) according to age and body mass index to supplementation with a daily 20-mL dose of OO either low or high in phenolics (18 compared with 286 mg caffeic acid equivalents per kg, respectively) for 6 wk. Urinary proteomic biomarkers were measured at baseline and 3 and 6 wk alongside blood lipids, the antioxidant capacity, and glycation markers. RESULTS: The consumption of both OOs improved the proteomic CAD score at endpoint compared with baseline (mean improvement: -0.3 for low-phenolic OO and -0.2 for high-phenolic OO; P < 0.01) but not CKD or diabetes proteomic biomarkers. However, there was no difference between groups for changes in proteomic biomarkers or any secondary outcomes including plasma triacylglycerols, oxidized LDL, and LDL cholesterol. CONCLUSION: In comparison with low-phenolic OO, supplementation for 6 wk with high-phenolic OO does not lead to an improvement in cardiovascular health markers in a healthy cohort.

Effects of oral vitamin C supplementation in hemodialysis patients: a proteomic assessment.

Evidence indicates that oxidative stress is present in dialysis patients, and is associated with vitamin C deficiency. Limited data are available regarding the effects of vitamin C supplementation on oxidative stress and inflammation markers in these patients. Moreover, there are no data available on plasma polypeptide fingerprints by proteome analysis before and after vitamin C supplementation. Therefore, we analyzed plasma samples from a prospective, randomized, open-labeled trial to assess the effects of oral vitamin C supplementation (250 mg three times per week), to define the plasma polypeptide pattern in hemodialysis patients. Our results reveal that more than 30 polypeptides show significant changes in the dialysis patients in comparison to controls with normal renal function, and that several polypeptides are affected/normalized by oral vitamin C supplementation. These results underline the remarkable potential for proteomics to recognize specific peptide profiles in different pathological situations, which might not be detected by classical methods.

PKC zeta enhances insulin-like growth factor 1-dependent mitogenic activity in the rat clonal beta cell line RIN 1046-38.

Protein kinase C seems to be linked to the regulation of insulin secretion as well as mitogenic signaling in pancreatic beta cells. To study the impact of different PKC isoforms on insulin secretion and mitogenic activity we stably overexpressed the PKC isoforms alpha, beta2, epsilon, and zeta in the rat clonal beta cell line RIN 1046-38. Under basal conditions PKC alpha, beta2, epsilon, and zeta were identified mainly in the cytosol. Treatment with the phorbol ester TPA caused translocation of PKC alpha, beta2, and epsilon to the plasma membrane. Glucose- and TPA-dependent increases in insulin release were comparable in all cell lines regardless of whether PKC was overexpressed or not. While PKC isoforms alpha, beta2, and epsilon had no effect on the [(3)H]thymidine incorporation rate, overexpression of PKC zeta specifically increased basal as well as IGF-1-dependent [(3)H]thymidine incorporation. Incubation with the MAP-kinase inhibitor PD98056 abolished this effect. Furthermore, treatment with IGF-1 led to activation of the beta cell-specific transcription factor PDX-1 in RIN 1046-38 cells overexpressing PKC zeta. Our data suggest that PKC zeta is involved in basal as well as IGF-1-dependent mitogenesis in RIN 1046-38 cells, while none of the PKC isoforms tested seem to be related to glucose-stimulated insulin release.