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BSE-associated prion-amyloid cardiomyopathy in primates.

Krasemann S, Mearini G, Krämer E, Wagenführ K, Schulz-Schaeffer W, Neumann M, Bodemer W, Kaup FJ, Beekes M, Carrier L, Aguzzi A, Glatzel M - Emerging Infect. Dis. (2013)

Bottom Line: Prion amyloidosis occurred in the heart of 1 of 3 macaques intraperitoneally inoculated with bovine spongiform encephalopathy prions.This macaque had a remarkably long duration of disease and signs of cardiac distress.Variant Creutzfeldt-Jakob disease, caused by transmission of bovine spongiform encephalopathy to humans, may manifest with cardiac symptoms from prion-amyloid cardiomyopathy.

View Article: PubMed Central - PubMed

Affiliation: University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

ABSTRACT
Prion amyloidosis occurred in the heart of 1 of 3 macaques intraperitoneally inoculated with bovine spongiform encephalopathy prions. This macaque had a remarkably long duration of disease and signs of cardiac distress. Variant Creutzfeldt-Jakob disease, caused by transmission of bovine spongiform encephalopathy to humans, may manifest with cardiac symptoms from prion-amyloid cardiomyopathy.

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Related in: MedlinePlus

Abundant PrPSc in heart of 1 bovine spongiform encephalopathy (BSE)–infected rhesus macaque. A) In sodium phosphotungstic acid precipitation of PrPSc, followed by Western blotting, highly abundant PrPSc was demonstrated in the heart of 1 BSE-infected primate. In this monkey, only the heart contained PrPSc. Controls include cardiac muscle spiked with minimal amounts brain of a healthy (–) and prion-diseased (+) primate. All analyses were prepared from 50 mg of tissue except the heart of 1 monkey 59 months postinoculation (mpi) (20 mg). PK, proteinase K. B) In protein-misfolding cyclic amplification, PrPSc was amplified only from the heart of 1 monkey 59 months postinoculation (mpi). As a positive control, brain tissue from a BSE-diseased monkey was used, and tissue from an uninfected control monkey served as a negative control. PK–digested hamster PrPSc (263 K) served as loading and digestion control for PrPSc. C) Paraffin-embedded tissue blotting of the entire heart of the 59 mpi monkey showed abundant deposition of PrPSc, mainly in the septum of the heart. Inset confirms the deposition pattern of PrPSc as amyloid. Scale bar = 0.25 mm. D) Histologic and immunohistochemical examination of heart tissue of the 59-mpi monkey by using hematoxylin and eosin (HE) staining and immunohistochemical staining against T-cell marker CD3 showed regularly configured cardiomyocytes and only single T-cells associated with blood vessels (arrow). Congo red staining showed Congo red–positive material in cardiomyocytes in a patch-like deposition pattern (arrows). Scale bar = 10 µm.
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Figure 2: Abundant PrPSc in heart of 1 bovine spongiform encephalopathy (BSE)–infected rhesus macaque. A) In sodium phosphotungstic acid precipitation of PrPSc, followed by Western blotting, highly abundant PrPSc was demonstrated in the heart of 1 BSE-infected primate. In this monkey, only the heart contained PrPSc. Controls include cardiac muscle spiked with minimal amounts brain of a healthy (–) and prion-diseased (+) primate. All analyses were prepared from 50 mg of tissue except the heart of 1 monkey 59 months postinoculation (mpi) (20 mg). PK, proteinase K. B) In protein-misfolding cyclic amplification, PrPSc was amplified only from the heart of 1 monkey 59 months postinoculation (mpi). As a positive control, brain tissue from a BSE-diseased monkey was used, and tissue from an uninfected control monkey served as a negative control. PK–digested hamster PrPSc (263 K) served as loading and digestion control for PrPSc. C) Paraffin-embedded tissue blotting of the entire heart of the 59 mpi monkey showed abundant deposition of PrPSc, mainly in the septum of the heart. Inset confirms the deposition pattern of PrPSc as amyloid. Scale bar = 0.25 mm. D) Histologic and immunohistochemical examination of heart tissue of the 59-mpi monkey by using hematoxylin and eosin (HE) staining and immunohistochemical staining against T-cell marker CD3 showed regularly configured cardiomyocytes and only single T-cells associated with blood vessels (arrow). Congo red staining showed Congo red–positive material in cardiomyocytes in a patch-like deposition pattern (arrows). Scale bar = 10 µm.

Mentions: Besides lymphoreticular tissues, the muscular compartment is targeted by prions (7,8). Thus, we assessed presence of PrPSc in skeletal and heart muscle by Western blot analysis with sodium phosphotungstic acid precipitation for enrichment of PrPSc and protein misfolding cyclic amplification by using published protocols (3). We could not detect substantial amounts of PrPSc in skeletal muscle (Figure 2, panel A). One macaque showed abundant PrPSc (≈1/100 of PrPSc found in brain) in heart in Western blot and protein misfolding cyclic amplification (Figure 2, panels A, B). Paraffin-embedded tissue blot analysis of this heart showed PrPSc as amyloid, occupying considerable stretches of heart tissue, mainly in the septum (Figure 2, panel C), whereas no PrPSc could be seen in hearts of other macaques (data not shown). These findings were confirmed by strong Congo red–positive patch-like depositions in cardiomyocytes in the heart of this monkey (Figure 2, panel D). The primate with cardiac PrPSc showed the longest disease duration (4 months, compared with 4 weeks for other BSE-infected monkeys), signs of cardiac affection when assessed by relevant makers of cardiac hypertrophy and of cardiac distress–associated inflammation, and only this macaque showed clinical signs of fatigue and signs of cardiac distress (i.e., venous congestion) on autopsy (Technical Appendix, Table). Histologic examination of heart tissue with hematoxylin and eosin staining and immunohistochemical stainings against B and T cells (CD20 [not shown] and CD3) did not provide evidence for toxic cardiomyopathy (i.e., fibrosis or vacuolization), nor did we find signs of inflammatory reaction (Figure 2, panel D).


BSE-associated prion-amyloid cardiomyopathy in primates.

Krasemann S, Mearini G, Krämer E, Wagenführ K, Schulz-Schaeffer W, Neumann M, Bodemer W, Kaup FJ, Beekes M, Carrier L, Aguzzi A, Glatzel M - Emerging Infect. Dis. (2013)

Abundant PrPSc in heart of 1 bovine spongiform encephalopathy (BSE)–infected rhesus macaque. A) In sodium phosphotungstic acid precipitation of PrPSc, followed by Western blotting, highly abundant PrPSc was demonstrated in the heart of 1 BSE-infected primate. In this monkey, only the heart contained PrPSc. Controls include cardiac muscle spiked with minimal amounts brain of a healthy (–) and prion-diseased (+) primate. All analyses were prepared from 50 mg of tissue except the heart of 1 monkey 59 months postinoculation (mpi) (20 mg). PK, proteinase K. B) In protein-misfolding cyclic amplification, PrPSc was amplified only from the heart of 1 monkey 59 months postinoculation (mpi). As a positive control, brain tissue from a BSE-diseased monkey was used, and tissue from an uninfected control monkey served as a negative control. PK–digested hamster PrPSc (263 K) served as loading and digestion control for PrPSc. C) Paraffin-embedded tissue blotting of the entire heart of the 59 mpi monkey showed abundant deposition of PrPSc, mainly in the septum of the heart. Inset confirms the deposition pattern of PrPSc as amyloid. Scale bar = 0.25 mm. D) Histologic and immunohistochemical examination of heart tissue of the 59-mpi monkey by using hematoxylin and eosin (HE) staining and immunohistochemical staining against T-cell marker CD3 showed regularly configured cardiomyocytes and only single T-cells associated with blood vessels (arrow). Congo red staining showed Congo red–positive material in cardiomyocytes in a patch-like deposition pattern (arrows). Scale bar = 10 µm.
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Related In: Results  -  Collection

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Figure 2: Abundant PrPSc in heart of 1 bovine spongiform encephalopathy (BSE)–infected rhesus macaque. A) In sodium phosphotungstic acid precipitation of PrPSc, followed by Western blotting, highly abundant PrPSc was demonstrated in the heart of 1 BSE-infected primate. In this monkey, only the heart contained PrPSc. Controls include cardiac muscle spiked with minimal amounts brain of a healthy (–) and prion-diseased (+) primate. All analyses were prepared from 50 mg of tissue except the heart of 1 monkey 59 months postinoculation (mpi) (20 mg). PK, proteinase K. B) In protein-misfolding cyclic amplification, PrPSc was amplified only from the heart of 1 monkey 59 months postinoculation (mpi). As a positive control, brain tissue from a BSE-diseased monkey was used, and tissue from an uninfected control monkey served as a negative control. PK–digested hamster PrPSc (263 K) served as loading and digestion control for PrPSc. C) Paraffin-embedded tissue blotting of the entire heart of the 59 mpi monkey showed abundant deposition of PrPSc, mainly in the septum of the heart. Inset confirms the deposition pattern of PrPSc as amyloid. Scale bar = 0.25 mm. D) Histologic and immunohistochemical examination of heart tissue of the 59-mpi monkey by using hematoxylin and eosin (HE) staining and immunohistochemical staining against T-cell marker CD3 showed regularly configured cardiomyocytes and only single T-cells associated with blood vessels (arrow). Congo red staining showed Congo red–positive material in cardiomyocytes in a patch-like deposition pattern (arrows). Scale bar = 10 µm.
Mentions: Besides lymphoreticular tissues, the muscular compartment is targeted by prions (7,8). Thus, we assessed presence of PrPSc in skeletal and heart muscle by Western blot analysis with sodium phosphotungstic acid precipitation for enrichment of PrPSc and protein misfolding cyclic amplification by using published protocols (3). We could not detect substantial amounts of PrPSc in skeletal muscle (Figure 2, panel A). One macaque showed abundant PrPSc (≈1/100 of PrPSc found in brain) in heart in Western blot and protein misfolding cyclic amplification (Figure 2, panels A, B). Paraffin-embedded tissue blot analysis of this heart showed PrPSc as amyloid, occupying considerable stretches of heart tissue, mainly in the septum (Figure 2, panel C), whereas no PrPSc could be seen in hearts of other macaques (data not shown). These findings were confirmed by strong Congo red–positive patch-like depositions in cardiomyocytes in the heart of this monkey (Figure 2, panel D). The primate with cardiac PrPSc showed the longest disease duration (4 months, compared with 4 weeks for other BSE-infected monkeys), signs of cardiac affection when assessed by relevant makers of cardiac hypertrophy and of cardiac distress–associated inflammation, and only this macaque showed clinical signs of fatigue and signs of cardiac distress (i.e., venous congestion) on autopsy (Technical Appendix, Table). Histologic examination of heart tissue with hematoxylin and eosin staining and immunohistochemical stainings against B and T cells (CD20 [not shown] and CD3) did not provide evidence for toxic cardiomyopathy (i.e., fibrosis or vacuolization), nor did we find signs of inflammatory reaction (Figure 2, panel D).

Bottom Line: Prion amyloidosis occurred in the heart of 1 of 3 macaques intraperitoneally inoculated with bovine spongiform encephalopathy prions.This macaque had a remarkably long duration of disease and signs of cardiac distress.Variant Creutzfeldt-Jakob disease, caused by transmission of bovine spongiform encephalopathy to humans, may manifest with cardiac symptoms from prion-amyloid cardiomyopathy.

View Article: PubMed Central - PubMed

Affiliation: University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

ABSTRACT
Prion amyloidosis occurred in the heart of 1 of 3 macaques intraperitoneally inoculated with bovine spongiform encephalopathy prions. This macaque had a remarkably long duration of disease and signs of cardiac distress. Variant Creutzfeldt-Jakob disease, caused by transmission of bovine spongiform encephalopathy to humans, may manifest with cardiac symptoms from prion-amyloid cardiomyopathy.

Show MeSH
Related in: MedlinePlus