A total of 930 subjects at high cardiovascular risk (420 men and 510 women) were recruited in the framework of a multicentre, randomized, controlled, parallel-group clinical trial directed at testing the efficacy of the TMD on the primary prevention of cardiovascular disease (The PREDIMED Study). Participants were assigned to a lowfat diet (control, n = 310) or one of two TMDs [TMD + virgin olive oil (VOO) or TMD + nuts]. Depending on group assignment, participants received free provision of extra-virgin olive oil, mixed nuts, or small non-food gifts. After 1 year of intervention, both TMDs decreased plasma N-terminal pro-brain natriuretic peptide, with changes reaching significance vs. control group (P < 0.05). Oxidized low-density lipoprotein decreased in both TMD groups (P < 0.05), the decrease in TMD + VOO group reaching significance vs. changes in control group (P = 0.003). Changes in lipoprotein(a) after TMD + VOO were less than those in the control group (P = 0.046) in which an increase (P = 0.035) was observed. No changes were observed in urinary albumin or albumin/creatinine ratio.

FVOOT improves HDL-subclass distribution and composition, and metabolism/antioxidant enzyme activities. FVOOT could be a useful dietary tool in the management of high cardiovascular risk patients.

This review describes the positive effects of growth hormone (GH) on the cardiovascular system. We analyze why the vascular endothelium is a real internal secretion gland, whose inflammation is the first step for developing atherosclerosis, as well as the mechanisms by which GH acts on vessels improving oxidative stress imbalance and endothelial dysfunction. We also report how GH acts on coronary arterial disease and heart failure, and on peripheral arterial disease, inducing a neovascularization process that finally increases flow in ischemic tissues. We include some preliminary data from a trial in which GH or placebo is given to elderly people suffering from critical limb ischemia, showing some of the benefits of the hormone on plasma markers of inflammation, and the safety of GH administration during short periods of time, even in diabetic patients. We also analyze how Klotho is strongly related to GH, inducing, after being released from the damaged vascular endothelium, the pituitary secretion of GH, most likely to repair the injury in the ischemic tissues. We also show how GH can help during wound healing by increasing the blood flow and some neurotrophic and growth factors. In summary, we postulate that short-term GH administration could be useful to treat cardiovascular diseases.

MicroRNAs (miRNAs) have emerged as promising biomarkers of disease. Their potential use in clinical practice requires standardized protocols with very low miRNA concentrations, particularly in plasma samples. Here we tested the most appropriate method for miRNA quantification and validated the performance of a hybridization platform using lower amounts of starting RNA. miRNAs isolated from human plasma and from a reference sample were quantified using four platforms and profiled with hybridization arrays and RNA sequencing (RNA-seq). Our results indicate that the Infinite® 200 PRO Nanoquant and Nanodrop 2000 spectrophotometers magnified the miRNA concentration by detecting contaminants, proteins, and other forms of RNA. The Agilent 2100 Bioanalyzer PicoChip and SmallChip gave valuable information on RNA profile but were not a reliable quantification method for plasma samples. The Qubit® 2.0 Fluorometer provided the most accurate quantification of miRNA content, although RNA-seq confirmed that only ~58% of small RNAs in plasma are true miRNAs. On the other hand, reducing the starting RNA to 70% of the recommended amount for miRNA profiling with arrays yielded results comparable to those obtained with the full amount, whereas a 50% reduction did not. These findings provide important clues for miRNA determination in human plasma samples.

The effect of circulating biomarkers in predicting coronary artery disease (CAD) is not fully elucidated. This study aimed to determine the relationship with CAD and the predictive capacity of nine biomarkers of inflammation (TNF-α, IL-10, IL-6, MCP-1, CRP), oxidation (GHS-Px), and metabolism (adiponectin, leptin, and insulin). This was a case-cohort study, within the REGICOR population-cohorts (North-Eastern Spain), of 105 CAD cases and 638 individuals randomly selected from a cohort of 5,404 participants aged 35–74 years (mean follow-up = 6.1 years). Biomarkers’ hazard ratio (HR)/standard deviation was estimated with Cox models adjusted for age, sex, and classical risk factors. Discrimination improvement and reclassification were analyzed with the c-index and the Net reclassification index (NRI). GHS-Px (adjusted HRs = 0.77; 95%CI:0.60–0.99), insulin (1.46; 1.08–1.98), leptin (1.40; 1.03–1.90), IL-6 (1.34; 1.03–1.74), and TNF-α (1.80; 1.26–2.57) were significantly associated with CAD incidence. In the model adjusted for all biomarkers, TNF-α (1.87;1.31–2.66) and insulin (1.59;1.16–2.19) were independently associated with CAD. This final model, compared to a model without biomarkers, showed a c-index difference of 1.3% (−0.7, 3.2) and a continuous NRI of 33.7% (2.6, 61.9). TNF-α and insulin are independently associated with CAD incidence and they improve reclassification when added to a model including classical risk factors.

This review describes the positive effects of growth hormone on the cardiovascular 13 system. We analyze why the vascular endothelium is a real internal secretion gland, whose 14 inflammation is the first step for developing atherosclerosis, as well as the mechanisms by which 15GH acts on the vascular endothelium improving its dysfunction. We also report how GH acts on 16 coronary arterial disease and heart failure, and on peripheral arterial disease inducing the 17 generation of new collateral vessels able to bypass a major artery occlusion. We include some 18 preliminary data from a trial in which GH or placebo is given to elder people suffering from critical 21We also analyze how Klotho may have strong relationships with GH, inducing, after being released 22 from the damaged vascular endothelium, the pituitary secretion of GH to repair the damaged tissue. 23Lastly, we show how GH induces wound healing by increasing the blood flow to the ischemic tissue. 24In summary, we postulate that short-time GH administration is useful for treating cardiovascular 25 diseases. 26

In Parkinson's disease, the efficacy of L-Dopa treatment changes over time, as dyskinesias emerge with previously beneficial doses. Using MitoPark mice, that models mitochondrial failure in dopamine (DA) neurons and mimics the progressive loss of dopamine observed in Parkinson’s disease, we found that the severity of DA denervation and associated adaptations in striatal neurotransmission at the time of initiation of L-Dopa treatment determines development of L-Dopa induced dyskinesias. We treated 20-week, and 28-week old MitoPark mice with L-Dopa (10 mg/kg i.p. twice a day) and found locomotor responses to be significantly different. While all MitoPark mice developed sensitization to L-Dopa treatment over time, 28-week old MitoPark mice with extensive striatal DA denervation developed abnormal involuntary movements rapidly and severely after starting L-Dopa treatment, as compared to a more gradual escalation of movements in 20-week old animals that started treatment at earlier stages of degeneration. Our data support that it is the extent of loss of DA innervation that determines how soon motor complications develop with L-Dopa treatment. Gene array studies of striatal neurotransmitter receptors revealed changes in mRNA expression levels for DA, serotonin, glutamate and GABA receptors in striatum of 28-week old MitoPark mice. Our results support that delaying L-Dopa treatment until Parkinson’s disease symptoms become more severe does not delay the development of L-Dopa-induced dyskinesias. MitoPark mice model genetic alterations known to impair mitochondrial function in a subgroup of Parkinson patients and provide a platform in which to study treatments to minimize the development of dyskinesia.

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