Department of Histology and Cytophysiology, Medical University of Białystok, Białystok, Poland.
Department of Neurosurgery, Medical University of Białystok, Białystok, Poland.
Biol Sex Differ. 2018 Nov 27;9(1):50. doi: 10.1186/s13293-018-0209-3.
Women live about 4 years longer due to lower prevalence of cardiovascular complication with ageing. However, the mechanisms involved in the preservation of heart functionality in women have not been fully elucidated. The endocannabinoid system fulfils a significant role in the regulation of cardiovascular system functioning. Cannabinoids, acting through specific receptors (CB1 and CB2), influence on blood pressure, heart rate and myocardial contractility. The function of cardiac muscle cells is strictly dependent on calcium ions. Calcium homeostasis in cardiomyocytes is subjected to complex regulation via calcium-binding proteins. Among them, increasing attention has been paid to the recently discovered S100A6 and CacyBP/SIP. In order to better understand sex differences in the regulation of cardiomyocyte function during ageing, we undertook the present research aimed at immunohistochemical identification and comparative evaluation of cannabinoid receptors, S100A6 and CacyBP/SIP, in the myocardium of ageing men and women.
The study was conducted on the hearts of 12 men and 10 women (organ donors) without a history of cardiovascular disease. The subjects were divided into two age groups: subjects older than 50 years and subjects under 50 years old. Paraffin heart sections were processed by immunohistochemistry for detection of cannabinoids receptors, S100A6 and CacyBP/SIP. In the heart samples from each study, participant's expression of genes coding for CB1, CB2, S100A6 and CacyBP/SIP using real-time PCR method was measured.
CB1 and CB2 immunoreactivity in the cytoplasm of cardiomyocytes in the heart of subjects over 50 was weaker than in younger individuals. In the heart of younger men, CB1-immunoreactivity was weaker and CB2-immunoreaction was stronger compared to women. In the hearts of older men, the CB1-immunostaining was more intense and CB2-immunoreactivity was weaker than in women. Immunodetection of CB1 shoved the presence of receptor in the intercalated discs, but only in the hearts of individuals over the 50 years old. In the hearts of older individuals, stronger immunolabelling was observed for S100A6 and CacyBP/SIP. Male hearts had greater S100A6-immunoreactivity (both age groups) but less CacyBP/SIP immunostaining (individuals over 50 years) compared to the age-matched women. The expression of genes coding CB1, CB2, S100A6 and CacyBP/SIP in the human heart was sex and age-dependent. Observed changes between men and women as well as between subject under and over 50 years were consistent with immunohistochemically stated changes in peptide content.
Together, the data presented here indicate a close interaction between ageing and sex on the distribution and levels of cannabinoid receptors (CB1, CB2), S100A6 and CacyBP/SIP in the human heart.
由于心血管并发症的患病率较低，女性的预期寿命比男性长约 4 年。然而，女性心脏功能保护的相关机制尚未完全阐明。内源性大麻素系统在心血管系统功能调节中起着重要作用。大麻素通过特定的受体（CB1 和 CB2）发挥作用，影响血压、心率和心肌收缩力。心肌细胞的功能严格依赖于钙离子。通过钙结合蛋白对心肌细胞中的钙离子稳态进行复杂的调节。其中，最近发现的 S100A6 和 CacyBP/SIP 受到了越来越多的关注。为了更好地理解衰老过程中心肌细胞功能调节中的性别差异，我们进行了本研究，旨在对衰老男性和女性心肌中大麻素受体、S100A6 和 CacyBP/SIP 进行免疫组织化学鉴定和比较评估。
本研究对 12 名男性和 10 名女性（器官捐献者）的心脏进行了研究，这些捐献者均无心血管疾病史。将研究对象分为两个年龄组：年龄大于 50 岁的组和年龄小于 50 岁的组。通过免疫组织化学方法检测心脏切片中的大麻素受体、S100A6 和 CacyBP/SIP。在每个研究的心脏样本中，使用实时 PCR 方法测量编码 CB1、CB2、S100A6 和 CacyBP/SIP 的基因的表达。
50 岁以上人群心肌细胞的 CB1 和 CB2 胞质免疫反应性弱于年轻个体。年轻男性的 CB1-免疫反应性较弱，而 CB2-免疫反应性较强。在老年男性的心脏中，CB1 免疫染色比女性更强烈，而 CB2 免疫反应性较弱。CB1 的免疫检测显示受体存在于闰盘，但仅存在于 50 岁以上的个体心脏中。在老年个体中，S100A6 和 CacyBP/SIP 的免疫标记更强。与年龄匹配的女性相比，男性心脏的 S100A6 免疫反应性更强（两个年龄组），但 CacyBP/SIP 免疫染色更弱（50 岁以上的个体）。人类心脏中编码 CB1、CB2、S100A6 和 CacyBP/SIP 的基因的表达存在性别和年龄依赖性。男性和女性之间以及 50 岁以下和 50 岁以上个体之间观察到的变化与肽含量的免疫组织化学变化一致。
综上所述，这些数据表明，在人类心脏中，大麻素受体（CB1、CB2）、S100A6 和 CacyBP/SIP 的分布和水平与衰老和性别之间存在密切的相互作用。
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