JTCS Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kennedy, J. H.
Right arrow Articles by Tedgui, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kennedy, J. H.
Right arrow Articles by Tedgui, A.

J Thorac Cardiovasc Surg 1998;115:238-239
© 1998 Mosby, Inc.

BRIEF COMMUNICATIONS

Increased calcium 45 fluxes in histologically abnormal humanascending aorta

J. H. Kennedy, MDa, D. Henrion, PhDb, M. Wassefc, MD, A. Piwnica, MDd, G. Bloch, MDd, A. Tedgui, PhDb


Paris, France, and Cambridge, United Kingdom

From INSERM U 141,b Service Central D'Anatomie etCytologie Pathologiques,c Service de Chirurgie Cardio-vasculaire,IFR "Circulation Lariboisiere,"d Hopital Lariboisiere,Paris, France, and The Babraham Institute,a Cambridge, UnitedKingdom.

Received for publication March 10, 1997; Accepted for publication August 8, 1997. Address for reprints: J. H. Kennedy, MD, The Babraham Institute,Cambridge CB2 4AT, United Kingdom.

Vascular calcium overload occurs during aging and is accelerated bysevere diabetes, smoking, and hypertension,Go 1associated with vascular structural changes such as coronary arterycalcification.Go 2 We hypothesizethat these vascular structural changes might be associated with change(s) incalcium turnover, which might lead to vascular disorders irrespective of age. Wetherefore studied, in vitro, the flux of 45Ca2+ inascending aortic wall obtained from 27 patients aged 7 to 84 years, mean 54.6(nine women), undergoing aortic valve replacement. No consent other than thatfor anesthesia and surgery was obtained. Ascending aortic wall was removed fromthe aortotomy; part was fixed in Bouin's solution and embedded in paraffin. Then4µm sections stained with Masson's trichrome stain were evaluated withoutknowledge of Ca2+ flux. Adventitia-free aortic segments were bathedin physiologic saline solution containing 45Ca2+ (296kBq/ml) for 120 minutes at room temperature to label the exchangeable Ca2+,according to the mehtod of Meisheri, Hwang, and van Breemen.Go 3 Tissues were transferred to ice-coldCa2+-free physiologic saline solution for 30 minutes to removeextracellular 45Ca2+.4 They were thenincubated overnight in ethylenediaminetetraacetic acid (2 mmol/L) at roomtemperature. Tissue and effluent were analyzed for 45Ca2+in a liquid scintillation counter. 45Ca2+ net uptake isexpressed as nanomoles per milligram weight. The ratio of 45Ca2+total uptake by the tissue to 45Ca2+ concentration inthe incubating bath, the distribution volume, was calculated. 45Ca2+efflux was expressed as percent total efflux, and efflux rate constant (perminute) was calculated from the total counts lost from the tissue during eachwashout period divided by the total counts remaining in the tissue segment.Go 4 Results were expressed as means ±standard error. The significance of the differences between means was determinedby the Student's t test (A. Tedgui).

Histologic findings in nine patients aged 26 to 83 years (mean 61.9years) were "normal for age"Go 5(Fig. 1). In 18 patients aged 7 to 86 years (mean52.9 years) histologic findings were considered abnormal (Fig. 2). The net uptake of 452+was significantly higher in samples of ascending aorta histologically abnormalthan in those histologically normal for age: 365 ± 36.8 nmol/mgtissue (n = 18) versus 244 ±37 nmol/mg tissue (n = 9,p < 0.05). The distribution volume forcalcium in histologically abnormal tissue was significantly greater than intissues normal for age: 2.4 ± 0.27 (n =18) versus 1.9 ± 0.27 (n = 9,p < 0.05). Efflux of 45CaGo 2 from the ascending aorta as percentof total as a function of time was 32.6% ± 4.5% (n = 18) versus 17.8% ± 3.5% (n = 9, p <0.04) at 1 and 2 minutes. 45Ca2+ efflux rate constantwas significantly increased in histologically abnormal tissue: 0.3 ±0.06 min-1 (n = 18) versus 0.14 ± 0.06 min-1(n =9, p < 0.05).



View larger version (117K):
[in this window]
[in a new window]
  		Fig. 1. Aorta, normal for agefrom a patient aged 76 years, showing mild initimal thickening and moderatefibrosis of the media (Masson's trichrome stain; original magnification x160).

 


View larger version (148K):
[in this window]
[in a new window]
  		Fig. 2. Aorta, showing atheroma(Masson's trichrome stain; original magnification x40).

 
Our study agrees with previous observations that atherosclerotic humanaorta binds more calcium in vivo than normal tissue.Go 5 45Ca2+ netuptake is an equilibrium between influx and efflux of Ca2+ in thearterial wall cells,Go 3 whereasvolume distribution represents the ratio of uptake by the tissue to 45Ca2+concentration in the incubating bath, corresponding to the accumulation of Ca2+in the arterial wall, including cells and matrix. That 45Ca2+net uptake was increased in tissues with abnormal histologic characteristicssuggests an increased accumulation in cells, without excluding an increasedaccumulation in the extracellular matrix, which would be responsible at least inpart for the increased distribution volume. 45Ca2+efflux can be divided into two phases. The initial loss of 45Ca2+represents mainly the washout of extracellular 45Ca2+.Efflux of 45Ca2+ occurring thereafter represents lossfrom intracellular sources. The increase in 45Ca2+effluxin tissues with abnormal histologic features and the increased 45Ca2+net uptake suggests an increased Ca2+ turnover in vessel wall.Change in Ca2+ homeostasis leads to vascular disorders by structuralchange, as observed in postmortem human aorta.

Our results suggest that histologically abnormal human ascending aorta isassociated with binding of Ca2+ irrespective of age.

Acknowledgments

We thank Professor Philippe Menasché for his assistancein this study.

Footnotes

J Thorac Cardiovasc Surg 1998;115:238-9

12/54/85373

References

  1. Fleckenstein A, Fleckenstein-Grun G, Frey M,Zorn J. Calcium antagonism and ACE inhibition. Am J Hypertens 1989;2:194-204. [Medline]
  2. Fitzpatrick LA, Severson A, Edwards WD,Ingraham RT. Diffuse calcification in human coronary arteries. J ClinInvest 1994;94:1597-604.
  3. Meisheri KD, Hwang O, van Breemen C. Evidencefor two separated Ca2 pathways in smooth muscle plasmalemma. JMembrane Biol 1981;59:19-25.[Medline]
  4. Henrion D, Bevan JA. Intraluminal flowpreferentially increases net sodium uptake in rabbit facial vein. J Vasc Res 1995;32:413-22.[Medline]
  5. Bouissou H, Pieraggi MT, Julian M. Agerelated morphological changes of the arterial wall. In: Camilleri JP, Berry CL,Fiessinger JN, Bariety J, editors. Diseases of the arterial wall. London:Springer Verlag; 1989. p. 77-8.




This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kennedy, J. H.
Right arrow Articles by Tedgui, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kennedy, J. H.
Right arrow Articles by Tedgui, A.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS