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. 2020 Nov;10(7):e213.
doi: 10.1002/ctm2.213.

Pulmonary paracoccidioidomycosis-induced pulmonary hypertension

Sabrina Setembre Batah  1 , Maiara Almeida Alda  1 , Juliana Rodrigues Machado-Rugulo  2 , Renato Gonçalves Felix  1 , Erika Nascimento  3 , Roberto Martinez  3 , Adriana Ignácio de Pádua  4 , Eduardo Bagagli  2 , Marluce Francisca Hrycyk  2 , Hélio Cesar Salgado  5 , Jaci Airton Castania  5 , Lourenço Sbragia  1 , Marcel Koenigkam Santos  6 , José Antônio Baddini-Martinez  4 , Sirlei Siani Morais  1 , Vera Luiza Capelozzi  7 , Rosane Duarte Achcar  8 , Alexandre Todorovic Fabro  1
Affiliations

Pulmonary paracoccidioidomycosis-induced pulmonary hypertension

Sabrina Setembre Batah et al. Clin Transl Med. 2020 Nov.
No abstract available

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Figures

FIGURE 1
FIGURE 1
Experimental pulmonary paracoccidioidomycosis induced pulmonary hypertension. After intrapulmonary injection of 1 × 108 paracoccidioidomycosis yeast, peribronchiolar well‐formed granulomas were seen (A). In contrast to controls (B, C, D), expanded adventitial layer of large (> 100 μm) (E), medium (50‐100 μm) (F), and small (<50 μm) (G) sized vessels were observed. Similarly, extracellular matrix deposition was present in peribronchiolar granulomas (H) and in all adventitial layer (L, M, N) compared to controls (I, J, K). RVSP was significantly higher in PCM subjects compared to the control group (O). Right ventricle to left ventricle plus septum (RV/LV+S) ratio was increased post‐PPCM infection, indicating increase in RV dilatation secondary to pulmonary hypertension (P). Precapillary vessels are decreased in PPCM compared to controls (Q). Collagen fraction is increased in all sizes of adventitial layer compared to controls (R) igual to adventitial diameter fraction, but not media (S). Perivascular collagen fibers deposition was directly correlated with an increase in mean pulmonary artery pressure in the PPCM group compared to the control group (P < .05) (T). Alfa smooth muscle actin (α‐SMA) immunoperoxidase stain (U) decorates vascular wall adventitial layer myofibroblastic activation (yellow arrows). This is further supported by transmission electron microscopy (V) identification of fibronexus (blue arrows) in adventitial layer. * P < .05
FIGURE 2
FIGURE 2
Human pulmonary paracoccidioidomycosis induced pulmonary hypertension. lung biopsy from PPCM patients and timeframe for development of pulmonary hypertension. Granulomas, expanded adventitial layer, and increased collagen fibers deposition in peri‐granuloma and perivascular areas were observed similar to animal model, highlighted by H&E and picrosirius red staining. Morphometrically, perivascular collagen fibers deposition was significantly increased in small (< 50 μm), medium (50‐100 μm), and large (>100 μm) sized vessels compared to the control group. Finally, two subsets of patients were established after PCM clinical cure (>2 years): (1) aggressive phenotype with progressive increase in RVSP; and (2) stable phenotype unassociated with progressive disease. δ P < .05
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