Naturally occurring left ventricular hyperplasia is a rare but lethal disease. There are very few reports of this cardiac disease in captive nonhuman primates. In a colony of Macaca mulatta (Rhesus monkey) at California National Primate Research Center, a large number of rhesus macaques were diagnosed by autopsy with naturally occurring left ventricular hypertrophy without obvious underlying diseases over a 22-year period. The confirmatory diagnosis of ventricular hypertrophy was based on findings of notable left ventricular concentric hypertrophy with reduced left ventricular lumen, which is very similar to human ventricular hypertrophy cases. This report discusses an 11-year-old Macaca fascicularis monkey (Cynomolgus monkey, crab-eating macaque), weighing 2.95 kg, that was presented for enrollment in a pharmacokinetic (PK) study. During the PK experiment, the monkey died following a sudden decrease in percutaneous oxygen saturation and heart rate. Gross and histological examinations of the heart were performed. On gross pathology, the left ventricular wall was thickened, and the chamber lumen was reduced. In histopathological examination using hematoxylin- eosin and Masson-trichrome stains, fibrosis and myocyte disarray were not observed, but an increased cell density, compared to the normal heart, was confirmed. The autopsy results confirmed left ventricular hyperplasia as the major cause of death.

To explore the role of histone deactylase (HDAC) activation in an in vivo model of hypertrophy, we studied the effects of Trichostatin A (TSA). TSA subjected to thoracic aortic banding (TAB)-induced pressure stress in mice. In histological observations, TAB in treated mice showed a significant hypertrophic response, whereas the sham operation remained nearly normal structure with partially blunted hypertrophy. TSA treatment had no effect (measured as HW/BW) on sham-operated animals. TAB animals treated with vehicle manifested a robust ～50% hypertrophic response (p<0.05 vs sham). TAB mice treated with 2 mg/kg/day TSA manifested a blunted growth responses, which was significantly diminished (p<0.05) compared with vehicle-treated TAB mice. TAB mice treated with a lower dose of TSA (0.5 mg/kg/day) manifested a similar blunting of hypertrophic growth (～25% increase in heart mass). Furthermore, to determine activity duration of TSA in vitro, 1 nM TSA was added to H9c2 cells. Histone acetylation was initiated at 4 hr after treatment, and it was peak up to 18 hr, then followed by significantly reduced to 30 hr. We also analyzed the expression of p53 following TSA treatment, wherein p53 expression was elevated at 4 hr, and it was maintained to 24 hr after treatment. ERK was activated at 8 hr, and maintained till 30 hr after treatment suggesting an intracellular signaling interaction between TSA and p53 expression. Taken together, it is suggested that HDAC activation is required for pressure-overload growth of the heart. Eventually, these data suggest that histone acetylation may be a novel target for therapeutic intervention in pressure-overloaded cardiac hypertrophy.

Our objective of current study was to investigate the development of bone and heart in association with diabetes mellitus (DM). DM was induced by administering an intraperitoneal injection of streptozotocin (STZ; 60 mg/kg) to 4‐gweek‐gold Sprague‐gDawley rats. Body weight and blood glucose were monitored, and rats were sacrificed after 2 or 5 weeks. The left ventricle (LV), including the interventricular septum, was weighed, and body weight and tibial bone length were assessed. Young diabetic rats showed reduced growth in terms of tibial length and body weight compared to controls. Moreover, diabetic males showed more significant growth suppression and reduced LV size than diabetic females. Morphometric analysis of tibiae from diabetic rats revealed suppressed bone growth at 2 and 5 weeks, with no difference between genders. STZ‐ginduced diabetes decreased bone growth and retarded pre‐gpubertal heart development. As a result, diabetes may increase cardiovascular risk factors and lead to eventual heart failure. Therefore, new therapeutic approaches are required for diabetic children exhibiting growth retardation. Heart growth factor, exercise, and cardiopulmonary physical therapy may be required to promote heart development and physiological function.

Mammalian spermatogenesis takes place in the seminiferousepithelium, which is composed of Sertoli cells and germ cells. The interaction between spermatogenic and Sertoli cells as well as elongated spermatids and Sertoli cells is tightly regulated by junctional adhesion molecules (JAMs). JAMs, which are cell adhesion molecules, are known to play roles in various biological processes such as fertilization, neurogenesis, cancer progression, and spermatogenesis. Members of the JAM family have a unique structure: they contain an N-terminal signal peptide domain, immunoglobulin (Ig)-like domains, transmembrane and cytoplasmic tail domains, each of which has distinct functions. The extracellular Ig-like domains interact in a homophilic or heterophilic manner, whereas cytoplasmic tail domain mediates the tight junction assembly. Although members of the JAM family are exclusively present in or restricted to the testis, their precise roles in spermatogenesis and fertilization have not yet been completely explored. The functional roles of Nectin-2, Nectin-3, JAM-C, cell adhesion molecule1 (CADM1), coxsackie and adenovirus receptor (CAR) have been evaluated by analysis of null mutant mice. Unfortunately, CAR-deficient mice had an embryonic lethal phenotype; this demonstrates the importance of CAR in development, but its physiological role in spermatogenesis is not known. The loss of CADM1, Nectin-3 and JAM-C resulted in male infertility caused by loss of adhesion between germ and Sertoli cells. A variety of JAMs participate in the interaction between germ and Sertoli cells. Recently, human VSIG1 has been characterized, which was originally known as A34, as a new member of the JAM family; VSIG1 is composed of two extracellular Ig-like domains, a transmembrane domain, and a cytoplasmic domain. However, this molecule has not been functionally characterized, so this was one of the aims of our present study. RT-PCR and immunoblot analyses were used to study VSIG1 expression, VSIG1 was specifically expressed in testicular germ cells but not in sperm. Pull-down assay with glutathione S-transferase (GST) or His-fused first Ig and second Ig domains of VSIG1 and SDS-PAGE under mild non-reducing conditions demonstrated that VSIG1 functions as an in vitro homophilic adhesion molecule. Furthermore, cells expressing a deletion of the C-terminus of VSIG1 failed to interact with ZO-1, the central structural protein of the tight junction. These findings suggest mouse VSIG1 interacts with an unknown molecule in Sertoli cells via its extracellular domain, while its cytoplasmic domain is needed for binding to ZO-1. Thus, we suggest mouse VSIG1 may play an important role in spermatogenesis rather than fertilization by forming heterophilic complex with a molecule similar to JAM family.