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Raffaele De Caterina

Publications and source records attributed to Raffaele De Caterina.

At least 19 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

The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKC epsilon inhibition.

A high intake of the omega-3 fatty acid docosahexaenoate [docosahexaenoic acid (DHA)] has been associated with systemic antiinflammatory effects and cardiovascular protection. Cyclooxygenase (COX)-2 is responsible for the overproduction of prostaglandins (PG) at inflammatory sites, and its expression is increased in atheroma. We studied the effects of DHA on COX-2 expression and activity in human saphenous vein endothelial cells challenged with proinflammatory stimuli. A>or=24-h exposure to DHA reduced COX-2 expression and activity induced by IL-1, without affecting COX-1 expression. DHA effect depended on the NF-kappaB-binding site in the COX-2 promoter. EMSAs confirmed that DHA attenuated NF-kappaB activation. Because MAPK, PKC, and NAD(P)H oxidase all participate in IL-1-mediated COX-2 expression, we also tested whether these enzymes were involved in DHA effects. Western blots showed that DHA blocked nuclear p65 NF-kappaB subunit translocation by decreasing cytokine-stimulated reactive oxygen species and ERK1/2 activation by effects on both NAD(P)H oxidase and PKCepsilon activities. Finally, to address the question whether DHA itself or DHA-derived products were responsible for these effects, we inhibited the most important enzymes involved in polyunsaturated fatty acid metabolism, showing that 15-lipoxygenase-1 products mediate part of DHA effects. These studies provide a mechanistic basis for antiinflammatory and possibly plaque-stabilizing effects of DHA.

Cells, Cultured↗
PubMed2006

Optical coherence tomography accurately identifies intermediate atherosclerotic lesions--an in vivo evaluation in the rabbit carotid artery.

OBJECTIVE: We tested the ability of optical coherence tomography (OCT) to identify very early stages of atherosclerosis in vivo. METHODS: Twelve New Zealand white male rabbits (weight 3.5-4.0 kg) underwent perivascular electrical injury of the common carotid arteries, and were then fed a cholesterol-rich diet. At 43+/-16 (range 27-63) days after injury, arteries were imaged by OCT, then rabbits were euthanized and vessels processed for histology. RESULTS: A total of 14 carotid arteries were imaged by OCT and histology; 22 atherosclerotic lesions were identified, 16 (73%) occurring at the site of the electrical injury. At histology, 4 lesions were defined as Stary type I (isolated macrophages), 8 as type II (intracellular lipid accumulations), and 10 as type III (small extracellular lipid pools). No advanced (> or =type IV) lesions were documented. OCT failed to detect any type I lesions, but correctly defined a minority (2/8, 25%) of type II lesions and the majority (8/10, 80%) of type III lesions. For type III lesions, sensitivity, specificity and diagnostic accuracy of OCT were 80%, 95%, and 95%, respectively. CONCLUSIONS: OCT can accurately detect intermediate (type-III) atherosclerotic lesions in vivo, but still fails to identify earlier stages of atherosclerosis.

Animals↗
PubMed2006

Trimetazidine improves post-ischemic recovery by preserving endothelial nitric oxide synthase expression in isolated working rat hearts.

OBJECTIVE: Previous investigations have consistently shown that the piperazine derivative trimetazidine (TMZ, 1-[2,3,4-trimethoxybenzil] piperazine, dihydrocloride) has cardioprotective effects in the experimental ischemia-reperfusion model. We tested the hypothesis that cardioprotective effect of TMZ is partly mediated by preservation of the endothelial barrier of the coronary microcirculation. METHODS: Isolated Wistar rat (250-300 g) hearts were subjected to a 15 min period of global ischemia and 180 min reperfusion in the presence or absence of 1 microM TMZ. Hemodynamic parameters, heart weight, creatinekinase (CK) release and microvascular permeability (FITC-albumin extravasation) were evaluated. In addition, eNOS gene expression was estimated by rt-PCR, and eNOS protein levels were assessed by Western analysis. In order to confirm the involvement of NO in mediating the cardioprotective effects of TMZ, 30 microM N(omega)-nitro-l-arginine methylester (L-NAME), a specific inhibitor of nitric oxide synthase, was used. RESULTS: After ischemia and reperfusion, TMZ produced a significant improvement of mechanical function associated with a reduction of CK release and FITC-albumin diffusion (P<0.001); the agent also resulted in improvement in coronary flow (at 45 min+27% vs control). The eNOS mRNA and protein levels were significantly higher in TMZ-treated hearts compared to controls. The addition of L-NAME significantly reduced the beneficial effects of TMZ on contractile function, CK release and FITC-albumin diffusion. CONCLUSIONS: in the isolated rat heart, TMZ exerts a relevant, NO-dependent, cardioprotection against ischemia-reperfusion injury and preserves the endothelial barrier of the coronary circulation. This could contribute to explain the cardioprotective action of TMZ following ischemia and reperfusion.

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

Rapid decline of collateral circulation increases susceptibility to myocardial ischemia: the trade-off of successful percutaneous recanalization of chronic total occlusions.

OBJECTIVES: We evaluated the time-behavior of changes in collateral circulation after successful percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in chronic (>1 month) total occlusions (CTO), and assessed their relationship with myocardial ischemia. BACKGROUND: It has been hypothesized that the immediate reduction of collateral flow after PCI of CTO could expose the patients to a higher risk of future ischemic events in the case of vessel reocclusion. METHODS: In 42 patients with CTO, two consecutive balloon inflations and final DES deployment were performed after positioning of a pressure guidewire. Minimal lumen diameter (MLD), diameter stenosis (DS), angiographic collateral grading (Rentrop score), myocardial (FFRmyo), coronary (FFRcor), and collateral fractional flow reserve (FFRcoll) were evaluated. Chest pain and the sum of ST-segment elevation (SigmaST) were analyzed to document the occurrence and extent of myocardial ischemia. RESULTS: Percutaneous coronary intervention induced a progressive improvement of indexes of stenosis severity (MLD, DS, Thrombolysis in Myocardial Infarction flow, FFRmyo, and FFRcor) and a rapid reduction in collateral circulation (FFRcoll and Rentrop score). A progressive worsening of ischemia at each balloon inflation occurred, concomitant with the reduction of collateral circulation. At linear regression analysis, an inverse relationship of FFRcoll with SigmaST (R2 = 0.352, p < 0.001) and angina pain score (R(2) = 0.247, p < 0.001) was observed. CONCLUSIONS: In CTO, collateral circulation, which provides most coronary flow at baseline, rapidly declines after successful stent implantation and the restoration of an antegrade flow. This rapid de-recruitment of collaterals is likely to put such patients at risk of future ischemic events.

Aged↗
PubMed2006

EMERALD, AIMI, and PROMISE: is there still a potential for embolic protection in primary PCI?

The recent trials of routine use of embolic protection devices for primary percutaneous coronary interventions (PCI) (the EMERALD, PROMISE, and AIMI trials) have demonstrated neutral or even negative effects of these devices on myocardial reperfusion and final infarct size. Despite these results, there is still ground to believe that PCI-induced embolization may be clinically relevant in specific subsets of patients with acute myocardial infarction (AMI). Significant clinical consequences may be expected when embolization is quantitatively relevant and/or is qualitatively characterized by lipid-rich athero-embolism (as is the case of lipid core embolization through the ruptured cap of a fibro-atheroma). Future trials on embolic protection devices in primary PCI should adopt a selective, rather than a routine strategy, through the identification, by angiographic or intravascular imaging parameters, of patients at highest risk of clinically relevant embolization. Such trials should also adopt specific endpoints able to evaluate the effect of micro-embolization, which is currently far from optimally assessed by the standard markers of myocardial reperfusion.

Angioplasty, Balloon, Coronary↗
PubMed2006

Celecoxib, ibuprofen, and the antiplatelet effect of aspirin in patients with osteoarthritis and ischemic heart disease.

BACKGROUND AND OBJECTIVE: We performed a placebo-controlled, randomized study to address whether celecoxib or ibuprofen undermines the functional range of inhibition of platelet cyclooxygenase (COX)-1 activity by aspirin in patients with osteoarthritis and stable ischemic heart disease. METHODS: Twenty-four patients who were undergoing long-term treatment with aspirin (100 mg daily) for cardioprotection were coadministered celecoxib, 200 mg twice daily, ibuprofen, 600 mg 3 times daily, or placebo for 7 days. RESULTS: The coadministration of placebo or celecoxib did not undermine the aspirin-related inhibition of platelet COX-1 activity, as assessed by measurements of serum thromboxane B(2) (TXB(2)) levels, as well as platelet function. In contrast, a significant (P < .001) increase in serum TXB(2) level was detected on day 7 before drug administration (median, 19.13 ng/mL [range, 1-47.5 ng/mL]) and at 24 hours after the coadministration of aspirin and ibuprofen (median, 22.28 ng/mL [range, 4.9-44.4 ng/mL]) versus baseline (median, 1.65 ng/mL [range, 0.55-79.8 ng/mL]); this was associated with a significant increase in arachidonic acid-induced platelet aggregation (P < .01) and adenosine diphosphate-induced platelet aggregation (P < .05) and a decrease in the time to form an occlusive thrombus in the platelet function analyzer (P < .01). The urinary excretion of 11-dehydro-TXB(2), an index of systemic thromboxane biosynthesis, was not significantly affected by the coadministration of treatment drugs. At steady state, a comparable and persistent inhibition of lipopolysaccharide-stimulated prostaglandin E(2) generation, a marker of COX-2 activity ex vivo, was caused by ibuprofen (>or=80%) or celecoxib (>or=70%) but not placebo. CONCLUSIONS: Unlike ibuprofen, celecoxib did not interfere with the inhibition of platelet COX-1 activity and function by aspirin despite a comparable suppression of COX-2 ex vivo in patients with osteoarthritis and stable ischemic heart disease.

Adenosine Diphosphate↗
PubMed2006

Aspirin overprescription in primary cardiovascular prevention.

INTRODUCTION: Aspirin overprescription is of some concern, especially in still-healthy individuals, and estimates of the magnitude of this problem are lacking. We evaluated the inappropriateness of aspirin prescription by primary care physicians in primary cardiovascular prevention. MATERIALS AND METHODS: Out of 20,599 patients screened by 16 primary care physicians in the Abruzzi region, central Italy, 400 patients were on treatment with aspirin for primary prevention. For each such patient, the absolute cardiovascular and coronary risks were assessed according to the Italian Cardiovascular Risk Chart for Primary Prevention and the European Society of Cardiology Coronary Risk Chart, respectively. Patients with a cardiovascular and/or coronary risk <1.0 event/100 patients/year were considered as treated inappropriately (aspirin overprescription), on the basis of previous literature. RESULTS: Overall, as many as 12% and 18% of patients had a cardiovascular and/or coronary risk <1.0 event/100 patients/year according to the European and the Italian charts, respectively, and therefore were defined as treated inappropriately. Patients with and without inappropriate treatment were similar with respect to smoking habits, family history and body max index. However, inappropriately treated patients had significantly lower levels of blood pressure and total cholesterol, and were more likely to be female, younger and non-diabetic than patients appropriately treated. CONCLUSIONS: A non-negligible proportion-up to 18%-of subjects in primary prevention is currently more likely to derive harm than benefit from inappropriate aspirin use. A wider use of Cardiovascular Risk Charts should guide primary care physicians in prescribing aspirin for primary prevention.

Aged↗
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↗
PubMed2006

Coronary arteriovenous fistula presenting as chronic pericardial effusion.

We here describe the incidental finding of a rare type of anomalous coronary artery, originating from the right coronary sinus of Valsalva and draining into the right ventricle, in a 72-year-old woman admitted to our hospital with a history of chronic pericardial effusion. The presence of a coronary artery fistula was suspected on transthoracic echocardiography, but diagnosed with the use of transoesophageal echocardiography and coronary angiography. Angiography allowed delineating the origin and course of the fistula, and its drainage into the right ventricle.

Aged↗
PubMed2006

[Myocardial infarction with normal coronary arteries: a condition with multiple etiology and variable prognosis].

Myocardial infarction with angiographically normal coronary arteries was recognized more than 30 years ago. Since then, various series of patients with such condition have been described, but the etiology and pathogenesis still remain a matter of debate. Evidence exists for a role of coronary vasospasm, thrombosis, embolization and inflammation, per se or combined, in determining the occurrence of myocardial infarction with angiographically normal coronary arteries. Endothelial dysfunction, possibly superimposed to non-angiographically evident atherosclerosis, may be an underlying common feature predisposing to the acute event. Additionally, myocarditis may explain some of these occurrences. Myocardial infarction with normal coronary arteries is therefore likely to be the result of multiple pathogenetic mechanisms. Although most reports emphasize the good prognosis of this condition, in general much better than myocardial infarction with coronary artery disease, prognosis is likely variable according to the underlying mechanism. This review summarizes current knowledge on this condition and examines areas of recent progress.

Coronary Aneurysm↗
PubMed2005

Recommendations for the management of patients after heart valve surgery.

Approximately 50,000 valve replacement operations take place in Europe annually and almost as many valve repair procedures. Previous European guidelines on management of patients after valve surgery were last published in 1995 and were limited to recommendations about antithrombotic prophylaxis. American guidelines covering the broader topic of the investigation and treatment of patients with valve disease were published in 1998 but devoted relatively little space to post-surgical management. This document represents the consensus view of a committee drawn from three European Society of Cardiology (ESC) Working Groups (WG): the WG on Valvular Heart Disease, the WG on Thrombosis, and the WG on Rehabilitation and Exercise Physiology. In almost all areas of patient management after valve surgery, randomized trials and meta-analyses do not exist. Such randomized trials as do exist are very few in number, are narrowly focused with small numbers, have limited general applicability, and do not lend themselves to meta-analysis because of widely divergent methodologies and different patient characteristics. Recommendations are therefore almost entirely based on non-randomized studies and relevant basic science.

Anticoagulants↗
PubMed2005

Contrasting effect of fish oil supplementation on the development of atherosclerosis in murine models.

OBJECTIVE: Increased fish oil intake is associated with protection against coronary heart disease and sudden death, while effects on atherosclerosis are controversial. We explored the effects of supplementing fish oil (rich in n-3 polyunsaturated fatty acids, PUFA) or corn oil (rich in n-6 PUFA) in two different models of atherosclerosis. METHODS AND RESULTS: Sixty-three low density lipoprotein receptor-deficient (LDLR(-/-)) mice and sixty-nine apolipoprotein E-deficient (apoE(-/-)) mice were fed diets without supplementations or supplemented with either 1% fish oil or 1% corn oil. In apoE(-/-) mice, neither fish oil nor corn oil had any major impact on plasma lipids or atherosclerosis. In LDLR(-/-) mice, conversely, the fish oil and the corn oil group had lower levels of LDL-cholesterol and triglycerides and had lesser atherosclerosis in the aortic root and in the entire aorta (p < 0.01 versus unsupplemented group). Atherosclerosis was significantly less in the fish oil group compared with the corn oil group when evaluated en face in the aortic arch (area positive to lipid staining: 32% with fish oil versus 38% with corn oil; 48% with unsupplemented diet). CONCLUSIONS: n-3 and n-6 PUFA supplementation retarded the development of atherosclerosis in LDLR(-/-) mice, with a stronger effect seen with n-3 PUFA. There was an important strain-dependence of the effect, with no protection against atherosclerosis in apoE(-/-) mice.

Animals↗
PubMed2005

At least 2 distinct pathways generating reactive oxygen species mediate vascular cell adhesion molecule-1 induction by advanced glycation end products.

OBJECTIVE: The interaction of advanced glycation end products (AGEs) with their main receptor RAGE in endothelial cells induces intracellular generation of reactive oxygen species (ROS) and the expression of vascular cell adhesion molecule (VCAM)-1. We investigated the role of distinct sources of ROS, including the mitochondrial electron transport chain, NAD(P)H oxidase, xanthine oxidase, and arachidonic acid metabolism, in AGE-induced VCAM-1 expression. METHODS AND RESULTS: The induction of ROS and VCAM-1 by AGEs in cultured human umbilical vein endothelial cells was specifically blocked by an anti-RAGE antibody. The inhibition of NAD(P)H oxidase by apocynin and diphenylene iodonium, and of the mitochondrial electron transport system at complex II by thenoyltrifluoroacetone (TTFA), significantly inhibited both AGE-induced ROS production and VCAM-1 expression, whereas these effects were potentiated by rotenone and antimycin A, specific inhibitors of mitochondrial complex I and III, respectively. The inhibition of Cu/Zn superoxide dismutase inhibited both ROS and VCAM-1 induction, indicating that H2O2 by this source is involved as a mediator of VCAM-1 expression by AGEs. CONCLUSIONS: Altogether, these results demonstrate that ROS generated by both NAD(P)H-oxidase and the mitochondrial electron transport system are involved in AGE signaling through RAGE, and indicate potential targets for the inhibition of the atherogenic signals triggered by AGE-RAGE interaction.

Arachidonic Acid↗
PubMed2005

Complete myocardial revascularization: between myth and reality.

Myocardial revascularization in patients with multi-vessel coronary artery disease may be accomplished, by percutaneous interventions or surgery, either on all diseased lesions or directed to selectively targeted coronary segments. The extent of planned revascularization is often a major determinant of treatment strategy. Revascularization of all diseased coronary segments-complete myocardial revascularization-has a potential long-term benefit, but is more complex and may increase in-hospital untoward events. Revascularization may otherwise be incomplete, either because of the operator's inability to treat all diseased coronary segments or by choice of deciding to selectively revascularize only large areas of myocardium at risk. Although incomplete revascularization may negatively affect long-term outcomes, it may be, when wisely chosen, the preferred treatment strategy in selected patient categories because of its lower immediate risks. The patient's clinical status, ventricular function, and the presence of co-morbidities may orient clinical decisions in favour of incomplete revascularization.

Angioplasty, Balloon, Coronary↗