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Biomedical subjects

Rosalinda Madonna

Publications and source records attributed to Rosalinda Madonna.

10 recordsLinked to original sources
PubMed2026

Genomic and proteogenomic insights into Spontaneous Coronary Artery Dissection (SCAD): A systematic review of emerging multi-omic evidence.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a major cause of myocardial infarction in young women without traditional cardiovascular risk factors (Hayes et al., 2018; Adlam et al., 2018 [1, 2]). Despite growing awareness, its biological underpinnings remain incompletely understood, and clinical management is largely based on observational evidence rather than mechanistic insight (Saw et al., 2014; Lettieri et al., 2015; Steg et al., 2024 [3-5]). OBJECTIVES: To systematically integrate genomic, epitranscriptomic, proteomic, and metabolomic data in order to characterize the multi-omic architecture of SCAD and identify potential biomarkers and therapeutic targets. METHODS: A systematic review was conducted in accordance with the PRISMA 2020 statement (Arbelo et al., 2023 [6]). PubMed/MEDLINE was searched for original studies investigating genomic and multi-omic features of SCAD. Data were extracted on study design, patient characteristics, identified variants, circulating biomarkers, and implicated biological pathways. Functional enrichment analysis was performed using the DAVID bioinformatics resource (Page et al., 2021 [7]). RESULTS: A total of 16 studies were included. Genome-wide association studies consistently identified susceptibility loci related to arterial structure and extracellular matrix integrity, including ADAMTSL4, PHACTR1/EDN1, LRP1, and FBN1 (Huang et al., 2009; Saw et al., 2020; Turley et al., 2020 [8-10]). Rare variant analyses further supported the role of genes involved in extracellular matrix remodeling and vascular smooth muscle cell function, including COL3A1, COL4A1/2, SMAD3, and TLN1 (Adlam et al., 2023; Turley et al., 2021, 2019; Carss et al., 2020; Zekavat et al., 2022; Wang et al., 2022 [11-16]), while ancestry-specific signals such as TSR1 variants were observed in distinct populations (Turley et al., 2023 [17]). Proteogenomic approaches linked genetic susceptibility loci to circulating proteins involved in matrix remodeling and inflammation, including cathepsin B and ECM1 (Maioli et al., 2010 [18]). Epitranscriptomic analyses identified differential microRNA expression profiles associated with vascular injury and repair pathways (Sun et al., 2019 [19]). CONCLUSIONS: SCAD is characterized by a complex, multi-layered biological architecture involving genetic susceptibility, extracellular matrix dysregulation, and vascular signaling pathways. Integration of multi-omic data provides novel insights into disease mechanisms and highlights potential biomarkers and targets for precision medicine approaches in SCAD.

Animals↗
PubMed2006

Prostacyclin improves transcoronary myocardial delivery of adipose tissue-derived stromal cells.

AIMS: Heart transplantation of adipose tissue-derived stromal cells (ADSCs) is under evaluation as a therapy for cardiac repair. Prostacyclin (PGI2), a vasodilator with additional effects on platelet aggregation and blood cell adhesion, exerts cardioprotection and might favour the myocardial delivery of ADSCs. We investigated the engraftment and influence on cardiac function of the transcoronary delivery of ADSCs and the effects of PGI2 compared with nitroglycerin (NTG) and adenosine (Ado) in isolated-perfused mouse hearts. METHODS AND RESULTS: Infusion of ADSCs at <1 x 10(6) cells/mL caused no significant changes in contractility and rhythm, whereas higher cell doses caused cardiac dysfunction. Perfusion with PGI2, NTG, and Ado concentration-dependently increased coronary flow (CF). Perfusion with PGI2, at variance from NTG and Ado, increased ADSC delivery and entrance into the myocardial interstitium without affecting ventricular or metabolic functions and CF (engrafted ADSCs, as percentage of control, at doses producing 50% of maximum vasodilation: PGI2: 220+/-12, P < 0.001; NTG: 110+/-8, P = N.S.; Ado: 80+/-5, P = N.S.). CONCLUSION: PGI2 safely increases myocardial delivery of ADSCs, by mechanisms independent of its vasodilatory properties, with a potential for its use in cell therapy for cardiac repair.

Adipose Tissue↗
PubMed2006

Nutritional mechanisms that influence cardiovascular disease.

Current evidence suggests that most significant risk factors for heart disease have been identified. Although age, sex, and genetics are important unmodifiable risk factors, most new cases of acute myocardial infarctions today can be predicted by the presence and level of 9 risk (or cardioprotective) factors that can easily be assessed and, most importantly, modified. These risk factors are the same in almost every geographic region and in every racial/ethnic group worldwide and are consistent in men and women. Eight of these 9 risk factors are influenced by diet, and most act by promoting atherogenesis, which is the most important background condition for cardiovascular disease. Dietary interventions mostly affect atherogenesis by modulating, at the cellular level, proinflammatory processes that initiate and perpetuate endothelial dysfunction, plaque formation, and, eventually, plaque rupture. For example, there is now enough evidence, both epidemiologic and clinical, of the beneficial effects of n-3 fatty acids. Either as part of a normal low-fat diet or as supplements, these fatty acids are now recommended to prevent cardiovascular disease. This review will summarize the mechanisms by which diet may influence atherogenesis through the early inception, progression, and clinical emergence of atherosclerosis, with a special focus on n-3 fatty acids.

Adult↗
PubMed2005

Simvastatin attenuates expression of cytokine-inducible nitric-oxide synthase in embryonic cardiac myoblasts.

Cardiac stem cells or myoblasts are vulnerable to inflammatory stimulation in hearts with infarction or ischemic injury. Widely used for the prevention and treatment of atherosclerotic heart disease, the cholesterol-lowering drugs statins may exert anti-inflammatory effects. In this study, we examined the impact of inhibition of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase with simvastatin on the expression of inducible nitric-oxide synthase (iNOS) in embryonic cardiac myoblasts stimulated with the proinflammatory cytokines, interleukin-1 or tumor necrosis factor. Treatment with simvastatin significantly reduced the levels of iNOS mRNA and protein in cytokine-treated rat H9c2 cardiac embryonic myoblasts. Addition of the HMG-CoA reductase product, L-mevalonate, and the by-product of cholesterol synthesis, geranylgeranyl pyrophosphate, could reverse the statin inhibitory effect on iNOS expression. Simvastatin treatment lowered the Rho GTPase activities, whereas the Rho-associated kinase inhibitor Y27632 partially blocked the statin inhibitory effect on nitrite production in the cytokine-treated H9c2 cells. Treatment with simvastatin led to inactivation of NF-kappaB by elevation of the NF-kappaB inhibitor IkappaB and reduction of the NF-kappaB nuclear contents in the cytokine-stimulated H9c2 cells. Hence, treatment with simvastatin can attenuate iNOS expression and NO synthesis in cytokine-stimulated embryonic cardiac myoblasts. The statin inhibitory effect may occur through isoprenoid-mediated intracellular signal transduction, which involves several key signal proteins, such as Rho kinase and IkappaB/NF-kappaB. These data suggest that statin therapy may protect the cardiac myocyte progenitors against the cytotoxicity of cytokine-induced high output of NO production in infarcted or ischemic hearts with inflammation.

Animals↗
PubMed2004

Effects of omega-3 fatty acids on cytokines and adhesion molecules.

The dietary intake of omega-3 (n-3) polyunsaturated fatty acids has emerged, over the past 20 years, as an important way to modify cardiovascular risk. This likely occurs through beneficial effects at all stages in the natural history of vascular disease, from the inception of atherosclerotic lesions, to their growth and acute complications (plaque rupture in most instances), up to protection of myocardium from the consequences of ensuing acute myocardial ischemia. This review specifically focuses on the modulating effects of n-3 fatty acids on biologic events involved in early atherogenesis, including important properties of these natural substances on endothelial expression of adhesion molecules and cytokines, processes collectively denoted as "endothelial activation." By decreasing the endothelial responsiveness to proinflammatory and proatherogenic stimuli, n-3 fatty acids act on molecular events not targeted by any other drugs or interventions, and thereby complementary to those of already implemented pharmacologic treatments.

Arteriosclerosis↗
PubMed2004

New cardiovascular risk factors: homocysteine and vitamins involved in homocysteine metabolism.

Among various cardiovascular risk factors, hyperhomocysteinemia has recently emerged as an important one. While there are currently no doubts on the relationship between severe hyperhomocysteinemia and vascular disease, some uncertainty still persists on the relationship between mild hyperhomocysteinemia and vascular disease. Several group B vitamins, namely vitamin B6, vitamin B12, and folate, influence homocysteine metabolism, being cofactors of the main metabolic pathways which allow the disposal of this amino acid. There are also, however, suggestions from the literature that group B vitamins, and in particular vitamin B6 (pyridoxine/pyridoxal-phosphate), are modulators of cardiovascular risk independent of homocysteine. The results of a recent study of ours, with a long follow-up, indeed suggest that homocysteine and vitamin B6 are independent and additive cardiovascular risk factors.

Biomarkers↗
PubMed2003

Antiarrhythmic effects of omega-3 fatty acids: from epidemiology to bedside.

Omega-3 polyunsaturated fatty acids are emerging as a safe and effective means to reduce sudden death after acute myocardial infarction. This review summarizes the epidemiological background for the use of omega-3 fatty acids with this indication, clinical trials performed so far, and experimental data supporting their antiarrhythmic efficacy.

Animals↗
PubMed2002

[Antiarrhythmia effects of omega-3 fatty acids. A review].

Omega-3 polyunsaturated fatty acids have been effective in reducing cardiovascular mortality in the recent GISSI-Prevenzione study. In a post-hoc analysis of this study an important observation has been the reduction of sudden cardiac death. The hypothesis that a protection from sudden death occurs because of antiarrhythmic effects of omega-3 fatty acids is supported by studies on cellular and animal models. A few intervention studies before the GISSI-Prevenzione and several retrospective analyses of epidemiological studies, in which nutritional variables connected with the intake of omega-3 fatty acids had been recorded, also support such a hypothesis. This review critically summarizes this type of evidence and indicates current research directions for its further validation.

Arrhythmias, Cardiac↗