Changes Of The Histological Structure With Age Growth And The Expression Of HIF-1α And VEGF In Yak Heart

Yak is a special species living in the area above 3000 m high plateau, with the "boat of the plateau" laudatory name. Yaks have obtained genetic features of high-altitude hypoxia adaption at the physiological, morphological, and genetic levels. The adaptability of yaks to the harsh environment of the high plateau is especially interesting because exposure of other cattle to low oxygen levels cause Bovine high-moutain or Brisket disease characterized by pulmonary hypertension and right ventricular hypertrophy. Yaks living on the Qinghai Tibet Plateau demonstrate less sensitivity and good adaptability to hypoxia. At present, there were a large number of studies on lung vascular. Researchers found that lung vascular of yak has its own unique characteristics which could distinguish the cattle living at low altitude. At present, the research on blood vessels of yak heart mainly focuses on the study of capillary bed, anatomical structure of the artery and vein of heart. However, the age of the study on the aging of the coronary arteries is not detailed enough, the study only stay in the anatomical structure of heart, and there is a little information on the levels of protein expression of HIF-1α and VEGF following the birth of yaks, and during their maturation at high altitude. Hence, thirty-two yaks(1 day, 6 months, 1 year, 2 years, and 5 year old) were included, and immunoelectronmicroscopy, immunohistochemistry, and enzyme-linked immunosorbent assay(ELISA) were used. These results would be useful to help us understand how the heart adapts to life in a low oxygen environment and could provide insight into the adaptations of the human heart at high altitudes. The results show as follows:1. At different age stages, the ultastructure of cardiac muscle cells showed regular changes, mainly in the mitochondria, cell membrane and collagen fiber.2. The diameter of collagen fiber in 6 months old yak heart was the largest. The number of collagen type Ⅰwas increased gradually with the increase of age. At the age of 5 years old, the collagen type Ⅰwas predominant.3. At all stages, mitochondria varied in shape. Mitochondria aggregated around the nucleus, and the shape was circular in 1-day-old yaks. Elongated mitochondria scattered between the myofibrils and mitochondrial ridge, which were uniform and well distributed and were seen in 6-month-old yaks. The ridge of mitochondria became irregular; concentrated and loose areas were found in mitochondria in 5-year-old yaks. The activity of complexes I, II, and V increased with aging. However, the activity of complexes III and IV increased in yaks from the age of 1 day to 1 year, and then decreased with aging.4. In general, a strong positive immunostaining of HIF-1α protein was observed in the majority of endothelial cells and cardiac muscle cells. In contrast, no expression of VEGF protein was found in cardiac muscle cells. VEGF protein was not only observed in endothelial cells, but also in smooth muscle cells of the coronary arteries. In addition, the immunostaining was not observed in endothelial cells and smooth muscle cells of the coronary artery and cardiac muscle cells of the corresponding control sections. Immunogold labeling with silver enhancement showed the localization of HIF-1αprotein on the cytoplasm(strong signals) and nuclei(weak signals) of endothelial cells, and cytoplasm(strong signals) of cardiac muscle cells. However, no gold particles were found in smooth muscle cells of the coronary artery localized with HIF-1α, including smooth muscle cells moved to the vascular intima. In contrast, immunoelectronmicroscopy labeling showed the localization of VEGF protein in the nuclei and perinuclei of smooth muscle cells of the coronary artery, and no signals presented on the cardiac muscle cells. In addition, VEGF protein was also found in the cytoplasm(strong signals) and nuclei(weak signals) of endothelial cells.5. HIF-1αprotein significantly increased in the myocardium and coronary artery from 1-day-old to 2-year-old yak heart, and decreased in the 5-year-old yak heart. A significant difference was found between yaks of 1 day and 2 years in age. However, VEGF protein increased in the myocardium and coronary artery with aging. The largest value of VEGF presented in 5-year-old yaks; a significant difference was found between yaks of 1 day and 5 years in age. The values of HIF-1α and VEGF were bigger in the left ventricular wall than in the right ventricular wall, and the same were bigger in rami anterior descendants than in the left circumflex.6. A strong positive immunostaining of HSP27 and HSP70 was observed in the majority of endothelial cells and cardiac muscle cells. HSP70 also expressed in in smooth muscle cells of the coronary arteries. HSP27 gene had the highest expression in the left ventricle of all ages, followed by the right ventricle, the left atrium and the right atrium. The expression of HSP70 gene was higher in the left ventricle from the beginning of 6 month old yak. The expression levels of HSP27 and HSP70 genes were higher in the ventricle than in the atrium.