Damage to the Cardiovascular System Under the Influence of Parathyroid Hormone

Abstract

Mechanism of Cardiovascular Pathology Formation in Hyperparathyroidism

Abstract: The work is dedicated to the analysis of hyperfunction of the parathyroid hormone (PThH), which negatively affects the major pathways of the heart. The current statistics on cardiovascular diseases associated with the endocrine system are exceeded. Studying this topic will expand knowledge in the field of endocrinology and cardiology, allowing the construction of chains of pathogenetic mechanisms of cardiovascular damage and the prevention of early atherosclerosis, atrial fibrillation, myocardial hypertrophy, and others.

Keywords: PThG, hyperparathyroidism, cardiovascular system, PThH, Ca.

Materials and Methods:

Negative effects of PTh hyperfunction on the heart. The parathyroid gland (PThG) is a small gland located in the posterior region of the thyroid gland. Its role is to maintain a stable concentration of Ca in the body. It performs this function by secreting parathyroid hormone (PThH) into the blood. The disease caused by excessive secretion of this hormone is called hyperparathyroidism. Hyperparathyroidism (HPTh) is a clinical syndrome caused by an increase in the concentration of PThH in the blood serum, associated with the proliferation of parathyroid glands. This can occur due to the formation of both benign (adenoma, hyperplasia) and malignant (cancer) neoplasms. In HPTh , Ca is washed out of the bone, making it brittle, and irreversible changes may occur in the body, accompanied by osteoporosis. Washed-out Ca from the bone enters the blood. Increased Ca concentration in the blood leads to arterial atherosclerosis throughout the body, which can lead to hypertension, triggering a heart attack and stroke. Elevated Ca puts a load on the heart, resulting in atrial fibrillation and increased heart rate.

Research has shown that HPTh increases the risk of death from cardiovascular diseases (CVDs) because the imbalance of Ca and PThH affects the activity of the cardiovascular system.

Similarities with PThH components. It has been proven that there are parathyroid hormone-like peptides (PThHrP) in the human body, which perform some functions of PThH, as they have structural similarities. They are mainly produced in the atria, endothelial vessels, and to a lesser extent in the myocardium of the ventricle. Due to the similarity of the N-termini of PThH and PThHrP, they have the ability to bind to common receptors located on the membranes of osteoclasts and osteoblasts, including myocardial cells and smooth muscle cells of blood vessels.

Effects of PThH on cardiomyocytes. PThH affects the energy metabolism of cardiomyocytes through PThH/PThHrP receptors, thereby suppressing their spontaneous contraction. As a result, the content of creatine phosphate and ATP decreases.

Effect of PThH on the cardiovascular system via CaSR. There is a concept of calcium-sensitive receptors (CaSR) in the parathyroid glands, which are involved in the regulation of molecular and cellular processes. It has also been found that CaSRs are expressed in smooth muscle cells of blood vessels and endothelial cells, where they stimulate vascular tone and participate in the proliferation of smooth muscle cells. There is a hypothesis that in the smooth muscle of the vascular wall, CaSR performs a protective function in the development of vascular calcification and also plays a role in myocardial adaptation to ischemia.

Based on the above information, it can be concluded that PThG hyperfunction negatively affects the cardiovascular system, as it increases the level of Ca in the blood, thereby affecting the function of CaSR.

CVDs caused by thickening of vessel walls. Common cardiovascular diseases with HPT pathology are associated with thickening and stiffness of the vascular wall. The important value of the intima-media complex of the common carotid artery reflects the relationship with the risk factor for CVDs.

The thickening of the intima-media complex is usually accompanied by a decrease in the diameter of the vessel and an increase in the stiffness of the walls of the carotid arteries.

Excess PThH and hypercalcemia. Data analysis confirms that the increase in PThH and Ca is a cause of CVD risk and, with prolonged exposure to the body, may be accompanied by a high level of mortality. In some sources, examples of negative effects on the cardiovascular system of increased PThH and hypercalcemia are given. In such cases, the development of arterial hypertension, ischemia, myocardial infarction, and angina pectoris are observed.

Let's consider the reasons for the increase in blood pressure (BP) with HPTh.

Excessive production of PThH increases the concentration of endothelin-1 and interleukin-6, and also activates the secretion of collagen β‑1 and integrin in smooth muscle cells of blood vessels, resulting in paradoxical increase in BP. It is also noted that excess PThH activates the renin-angiotensin-aldosterone system (RAAS), thereby increasing the secretion of aldosterone in the cortical zone of the adrenal glands. The increase in aldosterone plays an important role in the pathogenesis of many CVDs, as it is associated with a high risk of developing left ventricular hypertrophy, atherosclerosis, and even sudden death.

Hypercalcemia also contributes to cardiovascular pathology. Excess Ca in the blood serum leads to shortening of QT intervals, which is the cause of arrhythmia. It is also noted that hypercalcemia leads to the occurrence of calcification of the heart valve apparatus and the myocardium itself, contributing to increased mortality among patients.

Conclusion: Based on the above data, it is worth noting that HPTh affects the major pathways of the heart and affects a number of mechanisms that negatively affect it. Imbalance of Ca homeostasis and excess PThH lead to changes in the functions and structures of the cardiovascular system, accumulation of Ca in the heart, and its high concentration in the blood. This leads to the development of a number of diseases such as ischemia, myocardial infarction, left ventricular hypertrophy, arrhythmia, atherosclerosis, etc. It is noted that after parathyroidectomy, the risk of mortality from CVDs decreases and allows us to hope for a favorable outcome.

Authors' Information:

1 Stolikov E.L., Khristulenko A.L., Gnilitskaya V.B., Krivishev V.B., Kalugina A.A. "Damage to the Cardiovascular System in Hyperparathyroidism: A Modern View of the Problem"

2 T.L. Karonova, K.A Pogoslin, L.G. Yanevskaya, O.D. Belyaeva, E.N. Grineva "Mechanisms of Damage to the Cardiovascular System in Diseases of the Parathyroid Glands" Russia, St. Petersburg, 2020, pp. 64-68.

3 Khidirova G.O, Tursunboeva Z. "Morphological changes in the cardiac muscles with hypofunction of the parathyroid glands" pages 195-196

4 Khidirova G.O "Morphological features of cardiac muscles in hyperparathyroidism" pages 679-683.