A role for archaeal organisms in development of atherosclerotic vulnerable plaques and myxoid matrices

PURPOSE: Vulnerable plaques are characterized by a myxoid matrix, necrotic lipidic core, reactive oxygen species, and high levels of microorganisms. Aerobic microbes such as Chlamydophila pneumoniae and Mycoplasma pneumoniae usually do not survive in oxidative stress media. Archaea are anaerobic microbes with powerful anti-oxidative enzymes that allow detoxification of free radicals whose presence might favor the survival of aerobic microorganisms. We searched for archaeal organisms in vulnerable plaques, and possible associations with myxoid matrix, chlamydia, and mycoplasma bodies. METHODS: Twenty-nine tissue samples from 13 coronary artherectomies from large excentric ostial or bifurcational lesions were studied using optical and electron microscopy. Infectious agents compatible with archaea, chlamydia, and mycoplasma were semiquantified using electron micrographs and correlated with the amounts of fibromuscular tissue, myxoid matrix, and foam cells, as determined from semi-thin sections. Six of the cases were also submitted to polymerase chain reaction with archaeal primers. RESULTS: All 13 specimens showed archaeal-compatible structures and chlamydial and mycoplasmal bodies in at least 1 sample. There was a positive correlation between extent of the of myxoid matrix and archaeal bodies (r = 0.44, P = 0.02); between archaeal and mycoplasmal bodies (r = 0.41, P = 0.03), and between chlamydial bodies and foam cells (r = 0.42; P = 0.03). The PCR test was positive for archaeal DNA in 4 of the 6 fragments. DISCUSSION: DNA and forms suggestive of archaea are present in vulnerable plaques and may have a fundamental role in the proliferation of mycoplasma and chlamydia. This seems to be the first description of apparently pathogenic archaea in human internal organ lesions.

PROPOSTA: Placas vulneráveis são caracterizadas por matriz mixomatosa, centro lipídico necrótico, espécies reativas de oxigênio e alto níveis de microorganismos. Micróbios aeróbicos como Chlamydophila pneumoniae e Mycoplasma pneumoniae usualmente não sobrevivem em meio de estresse oxidativo. Arquéias são microorganismos anaeróbicos com poderosas enzimas anti-oxidantes que permitem detoxificação de radicais livres e a presença delas poderia favorecer a sobrevivência de micróbios aeróbicos. Pesquisamos por elementos de arquéia em placas vulneráveis e sua possível associação com degeneração mixomatosa da matriz e aumento do número de clamídias e micoplasmas. MÉTODOS: Vinte e nove amostras de 13 produtos de aterotomia de lesões grandes e excêntricas de óstio ou bifurcação de coronárias foram estudadas pela microscopia óptica e eletrônica. Agentes compatíveis com arquéia, clamídia e micoplasma foram semiquantificados pela microscopia eletrônica e correlacionados com quantidade de tecido fibromuscular, matriz mixomatosa e células xantomatosas. Seis casos foram também submetidos à reação em cadeia da polimerase com oligonucleotídeos de arquéia. RESULTADOS: Os 13 casos foram positivos para estruturas sugestivas de arquéia, micoplasma ou clamídia, em pelo menos uma amostra. Houve correlação positiva entre intensidade de matriz mixomatosa versus arquéia (r=0.44, p=0.02); arquéia versus micoplasma (r=0.41, p=0.03) e clamídia versus células xantomatosas r=0,42; 0.03). PCR foi positiva para DNA de arqueia em 4 dos 6 fragmentos. DISCUSSÃO: DNA e formas compatíveis com arquéia estão presentes em placas vulneráveis e podem ter papel fundamental na proliferação de micoplasma e clamídia. Este parece ser o primeiro relato de arquéia aparentemente patogênica em lesões de órgãos internos humanos.

Morphometric analysis of the fate of secretory epithelial cells in the ventral lobe of the rat prostate during massive apoptosis

Orchiectomy causes marked, rapid involution of the prostatic secretory epithelium. Concurrently, macrophages, which in normal glands are small and rarely occur at the base of the secretory epithelium, increase in size and number. Apoptotic cells are engulfed by companion epithelial cells and also by macrophages. In secretory cells and macrophages, dense bodies progressively increase in number and store membranes derived from dead cells of the secretory epithelium. In this work, we examined the contributions of the various routes of disposal of demised secretory epithelial cells of the rat prostate, induced to enter in apoptosis by retrieval of androgen. Specifi cally, we sought to determine how much membrane surface area derived from apoptotic cells of the secretory epithelium could be stored in dense bodies, and how these data compared with the disposal of dead cells via the glandular lumen. Glands from unoperated controls (day 0) and from rats examined 12 h and 1, 2, 3, 4, 5, 6, 7, 8, and 9 days after orchiectomy were studied morphometrically. The total membrane surface area of rough and smooth endoplasmic reticulum, Golgi apparatus, mitochondria and vesicles declined from 6.75 x 103 ìm2 in non-castrated rats to 1.12 x 103 ìm2 nine days after castration. Similarly, the total surface area of the secretory epithelium decreased from 10.6 x 1011 ìm2 in non-castrated rats to 0.204 x 1011 ìm2 nine days after castration. Geometrical models revealed that 1 ìm3 of dense body accommodated at least 142 ìm2 of myelin-like membrane surface area. Three to four days after castration, the total volume of intramacrophage dense bodies peaked (~5 x 106 ìm3) and represented 1-2% of the volume of intraepithelial dense bodies (~4 x 108 ìm3). The minimum membrane surface area that could be stored in dense bodies of the secretory epithelium on post-castration days 0, 1, 2, 3, 4 and 9 was 1.4%, 9%, 16%, 23%, 28% and 44%, respectively, of the total membrane surface area of the...