Background Vascular endothelial growth factor A (VEGF-A) and P2-receptors (P2Rs) are involved in the pathogenesis of diabetic nephropathy. The processing of VEGF-A by matrix metalloproteinases (MMP) regulates its bioavailability. Since the ATP-induced release of MMP-9 is mediated by P2Rs, we investigated the effect of suramin on VEGF-A excretion in urine and the urinary activity of total MMP and MMP-9. Methods The effect of suramin (10 mg/kg, ip) on VEGF-A concentration in serum and its excretion in urine was investigated in streptozotocin (STZ)-induced diabetic rats over a 21-day period. The rats received suramin 7 and 14 days after a single STZ injection (65 mg/kg, ip). A 24-h collection of urine was performed on the day preceding the administration of STZ and the first administration of suramin and on the day before the end of the experiment. The VEGF-A in serum and urine, albumin in urine, and total activity of MMP and MMP-9 in urine were measured using immunoassays. Results Diabetic rats are characterized by a sixfold higher urinary excretion of VEGF-A. Suramin potentiates VEGF-A urinary excretion by 36% (p = 0.046) in non-diabetic and by 75% (p = 0.0322) in diabetic rats but it did not affect VEGF-A concentration in the serum of non-diabetic and diabetic rats. Urinary albumin excretion as well as total MMP and MMP-9 activity was increased in diabetic rats, but these parameters were not affected by suramin. Conclusion Suramin increases the urinary excretion of VEGF-A in normoglycemia and hyperglycaemia, possibly without the involvement of MMP-9. Suramin may be used as a pharmacological tool enhancing VEGF-A urinary secretion.

The improvement in the lifespan of individuals with Down syndrome (DS) has created interest in the context of the development of age-related diseases. Among them is atherosclerosis-based cardiovascular disease (CVD), which seems to be an especially urgent and important issue. The aim of the present study was to evaluate the lipid markers that may clarify cardiovascular risk profiles in individuals with DS. To this end, we analyzed lipid profile parameters, including lipoprotein(a) (Lp(a)) levels, protein composition, and the antioxidative properties of high-density lipoprotein (HDL), in 47 adolescents with DS and 47 individuals without DS. Compared with the control group (C), subjects with DS had significantly increased concentrations of low-density lipoprotein cholesterol (105 ± 31 vs. 90 ± 24 mg/dL, p = 0.014), non-high-density lipoprotein cholesterol (120 ± 32 vs. 103 ± 26 mg/dL, p = 0.006), and triglycerides (72 [55–97] vs. 60 [50–77] mg/dL, p = 0.048). We found that patients with DS were characterized by significantly higher Lp(a) levels (31.9 [21.5–54.3] vs. 5.2 (2.4–16.1) mg/dL, p < 0.001). In fact, 57% of individuals with DS had Lp(a) levels above 30 mg/dL, which was approximately four times higher than those in the control group (DS 57% vs. C 15%). Apart from decreased high-density lipoprotein cholesterol levels in the subjects with DS (53 ± 11 vs. 63 ± 12 mg/dL, p < 0.001), differences in parameters showing the quality of HDL particles were observed. The concentrations of the main proteins characterizing the HDL fraction, apolipoprotein A-I and apolipoprotein A-II, were significantly lower in the DS group (144 ± 21 vs. 181 ± 33 mg/dL, p < 0.001; 33 ± 6 vs. 39 ± 6 mg/dL, p < 0.001, respectively). No significant differences between the groups were observed for the concentration of paraoxonase-1 (DS 779 ± 171 vs. C 657 ± 340 ng/mL, p = 0.063), enzyme activities toward paraoxon (DS 219 [129–286] vs. C 168 [114–272] IU/L, p = 0.949), or phenyl acetate (DS 101 ± 20 vs. C 93 ± 21 kIU/L, p = 0.068). There were no differences in myeloperoxidase activity between the study groups (DS 327 [300–534] vs. C 426 [358–533] ng/mL, p = 0.272). Our results are the first to demonstrate an unfavorable lipid profile combined with higher Lp(a) levels and quality changes in HDL particles in individuals with DS. This sheds new light on cardiovascular risk and traditional healthcare planning for adolescents with DS.

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Bicuspid aortic valve (BAV) affects 0.5–2% of the general population and constitutes the major cause of severe aortic valve stenosis (AVS) in individuals ≤70 years. The aim of the present study was to evaluate the parameters that may provide information about the risk of AVS developing in BAV patients, with particular emphasis on lipoprotein(a) (Lp(a)), which is a well-recognized risk factor for stenosis in the general population. We also analyzed the impact of autotaxin (ATX) and interleukin-6 (IL-6) as parameters potentially related to the pathomechanism of Lp(a) action. We found that high Lp(a) levels (>50 mg/dL) occurred significantly more frequently in patients with AVS than in patients without AVS, both in the group below and above 45 years of age (p = 0.036 and p = 0.033, respectively). Elevated Lp(a) levels were also strictly associated with the need for aortic valve replacement (AVR) at a younger age (p = 0.016). However, the Lp(a) concentration did not differ significantly between patients with and without AVS. Similarly, we observed no differences in ATX between the analyzed patient groups, and both ATX activity and concentration correlated significantly with Lp(a) level (R = 0.465, p < 0.001 and R = 0.599, p < 0.001, respectively). We revealed a significantly higher concentration of IL-6 in young patients with AVS. However, this observation was not confirmed in the group of patients over 45 years of age. We also did not observe a significant correlation between IL-6 and Lp(a) or between CRP and Lp(a) in any of the analyzed groups of BAV patients. Our results demonstrate that a high level of Lp(a), greater than 50 mg/dL, may be a significant predictive factor for earlier AVR. Lp(a)-related parameters, such as ATX and IL-6, may be valuable in providing information about the additional cardiovascular risks associated with developing AVS.

Hypercholesterolemia and oxidative stress may lead to disturbances in the renal microvasculature in response to vasoactive agents, including P2 receptors (P2R) agonists. We investigated the renal microvascular response to diadenosine tetraphosphate (Ap4A), an agonist of P2R, in diet‐induced hypercholesteremic rats over 28 days, supplemented in the last 10 days with tempol (2 mM) or DL‐buthionine‐(S,R)‐sulfoximine (BSO, 20 mM) in the drinking water. Using laser Doppler flowmetry, renal blood perfusion in the cortex and medulla (CBP, MBP) was measured during the infusion of Ap4A. This induced a biphasic response in the CBP: a phase of rapid decrease was followed by one of rapid increase extended for 30 min in both the normocholesterolemic and hypercholesterolemic rats. The phase of decreased CBP was not affected by tempol or BSO in either group. Early and extended increases in CBP were prevented by tempol in the hypercholesterolemia rats, while, in the normocholesterolemic rats, only the extended increase in CBP was affected by tempol; BSO prevented extended increase in CBP in normocholesterolemic rats. MBP response is not affected by hypercholesterolemia. The hypercholesterolemic rats were characterized by increased urinary albumin and 8‐isoPGF2α excretion. Moreover, BSO increased the urinary excretion of nephrin in the hypercholesterolemic rats but, similar to tempol, did not affect the excretion of albumin in their urine. The results suggest the important role of redox balance in the extracellular nucleotide regulation of the renal vasculature and glomerular injury in hypercholesterolemia.