C-reactive protein is increased in patients with degenerative aortic valvular stenosis

Galante, Alberto; Pietroiusti, Antonio; Vellini, Marina; Piccolo, Paola; Possati, Gianfederico; Bonis, Michele De; Grillo, R; Fontana, Carla; Favalli, Cartesio

doi:10.1016/s0735-1097(01)01484-x

Cited by 173 publications

(110 citation statements)

References 31 publications

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“…Unlike in early atherosclerotic lesions, in the present study we were not able to detect mentionable amounts of CRP in early valvular cusp lesions (grade 1), using both immunohistochemical staining and gene expression analysis or RT‐PCR. Increasing extracellular staining was observed not before grade 2 aortic valve sclerosis and was rather impressive around calcified areas of 4 lesions consistent with increased CRP levels in sera of patients with aortic stenosis 39. Regardless, the lack of extracellular staining of CRP in early valvular cusp lesions (grade 1) in contrast to early atherosclerotic lesions is remarkable and might contribute to the disparities in the pathogenesis of both entities.…”

Section: Discussionmentioning

confidence: 59%

Enzymatically Modified Low‐Density Lipoprotein Is Present in All Stages of Aortic Valve Sclerosis: Implications for Pathogenesis of the Disease

Twardowski

Cheng

Michaelsen

et al. 2015

JAHA

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BackgroundWe have demonstrated previously that enzymatically degraded low‐density lipoprotein (eLDL) is an essential causative component for the initiation of atherosclerosis. Here, we investigated the different stages of human aortic valve sclerosis for the presence of eLDL and effectors of the innate immune system, as well as the interaction of eLDL with isolated valvular interstitial cells/myofibroblasts to discover possible pathways leading to aortic valve sclerosis.Methods and ResultsHuman aortic valvular tissue was obtained from 68 patients undergoing valve replacement surgery. Patients were classified into 3 groups (mild, moderate, or severe aortic valve sclerosis), and clinical data for statistical analysis were gathered from all patients. Immunohistochemical staining demonstrated extensive extracellular deposits of eLDL throughout all grades of aortic valve sclerosis. Complementary analysis of lipid composition revealed higher concentrations of the decisive components of eLDL (ie, unesterified cholesterol and linoleic acid) compared with internal control tissues. Further, the complement component C3d and terminal complement complexes colocalized with eLDL compatible with the proposal that subendothelially deposited eLDL is enzymatically transformed into a complement activator at early stages of valvular cusp lesion development. Gene expression profiles of proteases and complement components corroborated by immunohistochemistry demonstrated an upregulation of the protease cathepsin D (a possible candidate for LDL degradation to eLDL) and the complement inhibitor CD55. Surprisingly, substantial C‐reactive protein expression was not observed before grade 2 aortic valve sclerosis as investigated with microarray analysis, reverse transcription–polymerase chain reaction analysis, and immunohistochemistry. Finally, we demonstrated cellular uptake of eLDL by valvular interstitial cells/myofibroblasts.ConclusionsThe present study is a startup of a hypothesis on the pathogenesis of aortic valve sclerosis declaring extracellular lipoprotein modification, subsequent complement activation, and cellular uptake by valvular interstitial cells/myofibroblasts as integral players.

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Section: Discussionmentioning

confidence: 59%

Enzymatically Modified Low‐Density Lipoprotein Is Present in All Stages of Aortic Valve Sclerosis: Implications for Pathogenesis of the Disease

Twardowski

Cheng

Michaelsen

et al. 2015

JAHA

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“…Mycoplasma pneumoniae may stimulate the virulence of Chlamydia pneumoniae leading to an intense inflammatory process, resulting in debris of cellular membranes of the bacteria and host cells, with accumulation of oxidized LDL-cholesterol 28 and Lp(a) 8 and a local inflammatory process 29 . The presence of a large number of phospholipids from degraded membranes of Chlamydia pneumoniae and Mycoplasma pneumoniae is an adequate substrate for calcium deposition, culminating in calcification of the valve.…”

Section: Discussionmentioning

confidence: 99%

Chlamydia pneumoniae e Mycoplasma pneumoniae nos nódulos de calcificação da estenose da valva aórtica

Santos¹,

Pierri²,

Higuchi³

et al. 2005

Arq. Bras. Cardiol.

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“…Such an elevation of natriuretic peptides predict adverse clinical outcome, such as occurrence of symptoms in still asymptomatic patients or higher operative mortality or worse post-operative outcome (Bergler-Klein et al, 2004;Pedrazzini et al, 2008). Systemic inflammation, expressed by elevated plasma CRP levels, influence the clinical outcome in advanced stages of aortic stenosis whereas no correlation to the progression from aortic sclerosis to aortic stenosis could be found in the Cardiovascular Health Study (Galante et al, 2001;Novaro et al, 2007).…”

Section: Biomarkersmentioning

confidence: 99%

Asymptomatic Aortic Stenosis - Prognosis, Risk Stratification and Follow-Up

Paoli¹,

Dichtl²

2011

Aortic Stenosis - Etiology, Pathophysiology and Treatment

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C-reactive protein is increased in patients with degenerative aortic valvular stenosis

Abstract: Systemic signs of inflammation, similar to those found in atherosclerosis, are present in patients with degenerative aortic valve stenosis. They do not seem to be linked to C. pneumoniae or H. pylori infection.

Cited by 173 publications

References 31 publications

Enzymatically Modified Low‐Density Lipoprotein Is Present in All Stages of Aortic Valve Sclerosis: Implications for Pathogenesis of the Disease

Enzymatically Modified Low‐Density Lipoprotein Is Present in All Stages of Aortic Valve Sclerosis: Implications for Pathogenesis of the Disease

Chlamydia pneumoniae e Mycoplasma pneumoniae nos nódulos de calcificação da estenose da valva aórtica

Asymptomatic Aortic Stenosis - Prognosis, Risk Stratification and Follow-Up

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