LETTER TO THE EDITOR

Atherosclerosis in the Renaissance elite: Ferdinand I Kingof Naples (1431–1494)

Raffaele Gaeta & Valentina Giuffra & Gino Fornaciari

Received: 12 March 2013 /Accepted: 13 March 2013 /Published online: 29 March 2013# Springer-Verlag Berlin Heidelberg 2013

Dear Editor,Atherosclerosis is often considered a modern disease, associ-ated with contemporary lifestyle; however, vascular calcifica-tions and plaques have been identified in ancient humanremains, mainly in the Egyptian mummies of people belong-ing to the elite classes [1, 2].

Various factors have been considered in the pathogenesis ofatherosclerosis, including genetic predisposition and environ-mental factors such as obesity, exposure to smoke and com-position of diet that is rich in cholesterol and saturated fats [3].

The mummy of Ferrante I of Aragon (1431–1494), Kingof Naples and one of the most important personalities of theItalian Renaissance, was exhumed from its sarcophagus inthe monumental sacristy of the Basilica of San DomenicoMaggiore in Naples (southern Italy). The dry microclimaticconditions of the church, where several mummies of Re-naissance Aragonese princes and noblemen are preserved,as well as the substances used for embalming, favored anexcellent state of preservation of soft tissues and internalorgans.

A comprehensive autopsy was performed on the king’smummy, and different tissues were sampled.Macroscopically,the right common carotid artery appeared distorted and calci-fied, with an irregular and bumpy wall due to a severe athero-sclerosis; however, the lumen was open (Fig. 1a). Samples ofthe artery, rehydrated in Sandison’s solution, were stainedwith hematoxylin and eosin (H&E) and with Weigert’s meth-od for elastic fibers. Some frozen sections, 7-μm thick, wereplaced onto polylysine-coated slides and stained with Oil RedO solution, to identify neutral triglycerides and lipoid deposits.

Atherosclerosis was confirmed by the histological findingsin terms of an intense red core (Fig. 1b) of oil red-positiveamorphous material, surrounded by a foamy substance, i.e. theatheroma, lying on a well-preserved elastic wall (Fig. 1c–d).Some granular fragments of calcium were present at the pe-riphery of the vessel, with several empty spaces, in the form ofneedle-like lacunae, caused by crystals of cholesterol dissolvedby routine histological methods. This complicated plaque ul-cerated, with abundant foamy material circumferentially pro-truding in the lumen, which could have occluded the arteryeasily. The smooth muscle of the wall appeared to be largelyreplaced by fibrous tissue in the form of longitudinal stripesbetween the laminae, spaced out by minute empty areas. Theintima was no longer present, probably because of post mortaldecay. This is a clear picture of sclerosis and elastosis, withdisintegration of the elastic fibers and neoformation of theparietal collagen tissue.

An artistical representation of the king, a statue ofFerrante in advanced age sculpted by Guido Mazzoni in1492, 2 years before his death, shows the marked profileof a tortuous and salient temporal artery (Fig. 2), whichsuggests a severe and diffuse arteriopathy. Nevertheless,contemporary chronicles describe that he had a very activelifestyle with horse riding and hunting, which suggests thatthe cerebral circle functioned competently [4].

Furthermore, our macroscopic examination showed thatFerrante was obese, reflected in large cutaneous folds. Pre-vious studies have demonstrated that the king was affectedby a mucinous adenocarcinoma infiltrating the soft tissuesof the small pelvis. DNA analysis revealed the presence ofK-ras codon 12 mutation, confirming that the tumor was acolorectal adenocarcinoma. Mutation of the K-ras gene isassociated with exposure to chemical carcinogens, probablypresent in the diet [5].

The Italian Renaissance aristocratic classes had access toa wide variety of food resources. According to the historical

R. Gaeta (*) :V. Giuffra :G. FornaciariDivision of Paleopathology, Department of Translational Researchon New Technologies in Medicine and Surgery, University of Pisa,Via Roma 57,56126 Pisa, Italye-mail: gaeta-raffaele@libero.it

Virchows Arch (2013) 462:593–595DOI 10.1007/s00428-013-1400-x

data, their diet was based on meat and wine, occasionallyenriched by eggs and cheese and, on penitential occasions,by fish. The consumption of vegetables was scarce, and fruitwas almost totally absent from their alimentation [6].

Carbon- and nitrogen-stable isotope analysis (13C and 15N)was carried out on bone collagen from Ferrante. The values of12‰ (11.9) in δ15N and of −18.1 in δ13C indicate an intake oflarge quantities of meat and a reduced integration of marinefish in the diet [7].

The lifestyle and alimentary patterns consisted of a dietrich in saturated fat, as attested by Ferrante’s obesity. Thehistorical data and the paleonutritional studies performedindicate that the members of the Renaissance elite societywere exposed both to the risk of developing atherosclerosisand colorectal cancer.

The present case, which is a unique histological docu-ment of the Renaissance age, confirms that atherosclerosis isboth an ancient and contemporary disease related to envi-ronmental factors which include diet, lack of exercise andobesity, typical of individuals of wealthy classes.

Acknowledgments This work was supported by a grant from theARPA Foundation (www.fondazionearpa.it).

Conflict of interest The authors declare that they have no conflict ofinterest.

References

1. David AR, Kershaw A, Heagerty A (2010) Atherosclerosis and dietin ancient Egypt. Lancet 375(9716):718–719

2. Allam AH, Thompson RC, Wann LS et al (2011) Atherosclerosis inancient Egyptian mummies: the Horus study. J Am Coll Cardiol Img4:315–327

Fig. 1 Fragment of the rightcommon carotid artery ofFerdinand I (a); thin section ofthe atheroma with Oil Red Ostaining (×40) (b), H&Estaining (×25) (c), and H&Estaining (×40) (d)

Fig. 2 Portrait of Ferdinand I in the Lamentation of Guido Mazzoni(Church of Santa Maria dei Lombardi, Naples) (photo of the Divisionof Paleopathology, Pisa)

594 Virchows Arch (2013) 462:593–595

3. George SJ, Johnson J (2010) Atherosclerosis: molecular and cellularmechanisms. Weinheim, Wiley

4. Pontieri E (1969) Per la storia del regno di Ferrante I d’Aragona redi Napoli: studi e ricerche. Edizioni scientifiche italiane, Napoli

5. Ottini L, Falchetti M, Marinozzi S, Angeletti LR, Fornaciari G (2011)Gene-environment interactions in the pre-Industrial Era: the cancer ofKing Ferrante I of Aragon (1431–1494). Hum Pathol 42:332–339

6. Grieco AJ (1999) Food and social classes in late Medieval andRenaissance Italy. In: Montanari M (ed) Flandrin JL. Food. Aculinary history from antiquity to the present. Columbian UniversityPress, New York, pp 302–312

7. Fornaciari G (2008) Food and disease at the Renaissance courtsof Naples and Florence: a paleonutritional study. Appetite51:10–14

Virchows Arch (2013) 462:593–595 595