Forensic significance of intracardiac heme oxygenase-1 expression in acute myocardial ischemia

Yumi Kuninaka,Mitsunori Ozaki,Yuko Ishida,Emi Shimada,Akiko Ishigami,Hiroki Yamamoto,Fukumi Furukawa,Akihiko Kimura,Toshikazu Kondo,Akira Taruya,Mizuho Nosaka

doi:10.1038/s41598-021-01102-y

Yumi Kuninaka, Mitsunori Ozaki + Show 9 more

Open Access

https://doi.org/10.1038/s41598-021-01102-y

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Abstract

Heme oxygenase-1 (HO-1), an inducible stress-response protein, exerts anti-oxidant and anti-apoptotic effects. However, its significance in forensic diagnosis of acute ischemic heart diseases (AIHD) such as myocardial infarction (MI) is still unknown. We examined the immunohistochemical expression of HO-1 in the heart samples to discuss their forensic significance to determine acute cardiac ischemia. The heart samples were obtained from 23 AIHD cases and 33 non-AIHD cases as controls. HO-1 positive signals in cardiomyocyte nuclear were detected in 78.2% of AIHD cases, however, that were detected in only 24.2% control cases with statistical difference between AIHD and non-AIHD groups. In contrast to HO-1 protein expression, there was no significant difference in the appearance of myoglobin pallor regions and leukocyte infiltration in the hearts between AIHD and non-AIHD groups. From the viewpoints of forensic pathology, intracardiac HO-1 expression would be considered a valuable marker to diagnose AIHD as the cause of death.

Highlights

Heme oxygenase-1 (HO-1), an inducible stress-response protein, exerts anti-oxidant and antiapoptotic effects
Contraction bands could be confirmed by Masson trichrome staining in some of acute ischemic heart diseases (AIHD) groups (Fig. 1b), and there was a significant difference of percentage of the case where contraction band existed between AIHD and non-AIHD groups (52.1% vs. 9.0%, Fig. 1c)
As a method for detecting myocardial ischemia, visualization of molecular change by immunohistochemical examination has been proposed, but its application depends on the availability of a specific and sensitive m arker[15,26,27]

Summary

Results

HE staining showed that there was no specific histological sign of MI in both AIHD and non-AIHD groups (Fig. 1a and Supplemental Fig. 1). The immunohistochemical staining of myoglobin revealed no differences in the appearance of myoglobin pallor regions between AIHD and non-AIHD groups (Fig. 1d and Supplemental Fig. 2). In AIHD hearts, neutrophils and macrophages were observed to a similar extent as non-AIHD (Fig. 2). These observations implied that the evaluation of leukocyte recruitment would not be powerful clue for the diagnosis of early phase of AIHD. The comparison between AIHD and non-AIHD groups showed significant difference of the number of HO-1 expressed case (Fig. 3b). There were no significant differences on age, gender, or PMI for HO-1 protein expressions (Fig. 4)

Discussion

Methods

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