Giulia Driussi

Background/Objectives: Oxidative stress is a major contributor to the pathogenesis of cardiovascular diseases, including hypertension, ischemic cardiomyopathy, and heart failure. MicroRNAs (miRNAs) have been extensively investigated in various contexts, and some of them have been identified to play a role in cardiovascular disease. This narrative review focuses on miR-103 and miR-155, two miRNAs implicated in the modulation of oxidative stress and cardiovascular remodeling. Methods: The following queries were used in PubMed since inception until May 2026: ((“miR-155” OR “microRNA-155” OR miR155) AND (“oxidative stress” OR ROS OR “reactive oxygen species”) AND (“cardiovascular disease” OR cardiovascular OR cardiac OR heart OR vascular)); ((“miR-103” OR “microRNA-103” OR miR103) AND (“oxidative stress” OR ROS OR “reactive oxygen species”) AND (“cardiovascular disease” OR cardiovascular OR cardiac OR heart OR vascular)). Results: A total of seven citations for miR-103 and 79 citations for miR-155 were identified. Reviews and papers about diseases other than those on cardiac/vascular involvement were excluded. miR-155 emerges as a potential regulator of inflammatory-redox signaling, whereas miR-103 appears more closely linked to cell fate and metabolic pathways. In both cases, available evidence supports a context-dependent role that challenges simplistic classification as pro- or antioxidant miRNAs. Conclusions: Available evidence suggests that both miR-103 and miR-155 are important regulators of oxidative stress-related pathways in cardiovascular disease. Nevertheless, the context-dependent effects observed across different cardiovascular disorders raise concerns regarding the safety of systemic miRNA modulation-based therapeutic strategies. Future studies should clarify the determinants of this context-dependent behavior and identify the specific conditions under which these miRNAs exert protective or harmful effects, which might pave the way for the development of miRNA-based therapeutic strategies targeting oxidative stress and cardiovascular remodeling.

Background/Objectives: Oxidative stress is a major contributor to the pathogenesis of cardiovascular diseases including hypertension, ischemic cardiomyopathy, heart failure. MicroRNAs (miRNAs) have been extensively investigated in various contexts, and some of them have been identified to play a role in cardiovascular disease. This review focuses on miR-103 and miR-155, two miRNAs implicated in the modulation of oxidative stress and cardiovascular remodeling. Methods: The following queries were used in PubMed since inception until May 2026: (("miR-155" OR "microRNA-155" OR miR155) AND ("oxidative stress" OR ROS OR "reactive oxygen species") AND ("cardiovascular disease" OR cardiovascular OR cardiac OR heart OR vascular)); (("miR-103" OR "microRNA-103" OR miR103) AND ("oxidative stress" OR ROS OR "reactive oxygen species") AND ("cardiovascular disease" OR cardiovascular OR cardiac OR heart OR vascular)). Results: A total of 7 citations for miR-103 and 79 citations for miR-155 were identified. Reviews and papers about diseases other than those on cardiac/vascular involvement were excluded. miR-155 emerges as a potential regulator of inflammatory-redox signaling, whereas miR-103 appears more closely linked to cell fate and metabolic pathways. In both cases, available evidence supports a context-dependent role that challenges simplistic classification as pro- or anti-oxidant miRNAs. Conclusions: Available evidence suggests that both miR-103 and miR-155 are important regulators of oxidative stress-related pathways in cardiovascular disease. Nevertheless, the context-dependent effects observed across different cardiovascular disorders raise concerns regarding the safety of systemic miRNA modulation-based therapeutical strategies. Future studies should clarify the determinants of this context-dependent behavior and identify the specific conditions under which these miRNAs exert protective or harmful effects, which might pave the way for the development of miRNA-based therapeutic strategies targeting oxidative stress and cardiovascular remodeling.

Background: Oxidative stress (OxSt) and inflammation are common in CKD and are known CV and mortality risk factors. In peritoneal dialysis (PD) OxSt and Inflammation even increase due to the use of glucose‐based solutions.Patients and Methods: This study analyzed in 15 PD patients the effect of 3 and 6 months of treatment with icodextrin‐based glucose‐free solutions on OxSt and inflammation, evaluating p22^phox protein expression (Western blot), NADPH oxidase subunit, essential for OxSt activation, MYPT‐1 phosphorylation state, marker of RhoA/Rho kinase pathway (ROCK) activity, involved in the induction of OxSt (Western blot) and Malondialdehyde (MDA) production (fluorimetric assay). Interleukin (IL)‐6 blood level (chemiluminescence assay) has been measured and used as a marker of inflammation.Results: p22^phox protein expression, MYPT 1 phosphorylation, and MDA were reduced after 3 months from the start of icodextrin (1.28 ± 0.18 d.u. vs. 1.50 ± 0.19, p = 0.049; 0.89 ± 0.03 vs. 0.98 ± 0.03, p = 0.004; 4.20 ± 0.18 nmol/mL vs. 4.84 ± 0.32 nmol/mL, p = 0.045, respectively). In a subgroup of 9 patients who continued the treatment up to 6 months, MYPT‐1 phosphorylation was further reduced at 6 months compared to baseline (0.84 ± 0.06 vs. 0.99 ± 0.04, p = 0.043), while p22^phox protein expression was reduced only at 6 months versus baseline (1.03 ± 0.05 vs. 1.68 ± 0.22, p = 0.021). In this subgroup, MDA was reduced at 6 months versus baseline (4.03 ± 0.24 nmol/mL vs. 4.68 ± 0,32, p = 0.024) and also versus 3 months (4.03 ± 0.24 vs. 4.35 ± 0.21, p = 0.008). IL‐6 level although reduced both at 3 and 6 months, did not reach statistical significance.Conclusions: The reduction of OxSt with icodextrin‐based PD solutions, although obtained in a small patients cohort and in a limited time duration study, strongly supports the rationale of using osmo‐metabolic agents‐based fluids replacing glucose‐based fluids. Ongoing studies with these agents will provide information regarding preservation of peritoneal membrane integrity, residual renal function, and reduction of CVD risk factors such as OxSt and inflammation.

In the last two decades, the study of the renin–angiotensin–aldosterone system (RAAS) has revealed a counterregulatory protective axis. This protective arm is characterized by ACE2/Ang 1-7/MasR and Ang 1-9 that largely counteracts the classic arm of the RAAS mediated by ACE/Ang II/AT1R/aldosterone and plays an important role in the prevention of inflammation, oxidative stress, hypertension, and cardiovascular remodeling. A growing body of evidence suggests that enhancement of this counterregulatory arm of RAAS represents an important therapeutic approach to facing cardiovascular comorbidities. In this review, we provide an overview of the beneficial effects of ACE2, Ang 1-7/MasR, and Ang 1-9 in the context of oxidative stress, vascular dysfunction, and organ damage.

Fabry disease is a rare X-linked disease characterized by deficient expression and activity of alpha-galactosidase A (α-GalA) with consequent lysosomal accumulation of glycosphingolipid in various organs. Currently, enzyme replacement therapy is the cornerstone of the treatment of all Fabry patients, although in the long-term it fails to completely halt the disease’s progression. This suggests on one hand that the adverse outcomes cannot be justified only by the lysosomal accumulation of glycosphingolipids and on the other that additional therapies targeted at specific secondary mechanisms might contribute to halt the progression of cardiac, cerebrovascular, and renal disease that occur in Fabry patients. Several studies reported how secondary biochemical processes beyond Gb3 and lyso-Gb3 accumulation—such as oxidative stress, compromised energy metabolism, altered membrane lipid, disturbed cellular trafficking, and impaired autophagy—might exacerbate Fabry disease adverse outcomes. This review aims to summarize the current knowledge of these pathogenetic intracellular mechanisms in Fabry disease, which might suggest novel additional strategies for its treatment.