The key initiating process in atherogenesis is the subendothelial cholesterol retention, which is both necessary and sufficient to provoke lesion initiation. Retention of cholesterol transported by low density lipopro...The key initiating process in atherogenesis is the subendothelial cholesterol retention, which is both necessary and sufficient to provoke lesion initiation. Retention of cholesterol transported by low density lipoprotien (LDL) in subendothelial cells of arterial wall, is an absolute requirement for lesion development. This allows us to consider intracellular cholesterol retention as a novel target for anti-atherosclerotic therapy. In this case, the target is not the level of blood cholesterol but the level of cholesterol in vascular cells. This review summarizes the results of our basic studies shedding light on the mechanisms of intracellular cholesterol retention. We describe our cellular models to search for anti-atherosclerotic agents and demonstrate the use of these models for the development of anti-atherosclerotic drugs. We use natural products as the basis of anti-atherosclerotic drugs because anti-atherosclerotic therapy should be long-term or even lifelong. Using cellular models and natural products, we have developed an approach to prevent intracellular cholesterol retention in cultured subendothelial aortic cells. We have developed drugs that reduce intracellular cholesterol retention, namely Allicor on the basis of garlic powder, anti-inflammatory drug Inflaminat (calendula, elder, and violet) possessing anti-cytokine activity and phytoestrogen-rich drug Karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid). Treatment with Allicor or Inflaminat caused regression of carotid atherosclerosis in asymptomatic men. Karinat prevented the development of new atherosclerotic plaques in postmenopausal women. Thus, the main findings of our basic research have been successfully translated into clinics. As a result, this translation, a novel approach to the development of anti-atherosclerotic therapy, has been established. Our clinical trials have confirmed the suitability of innovative approach and the efficacy of novel drugs developed on the basis our methodology.展开更多
Accumulation of cholesterol in arterial cells, intracellular cholesterol retention, may be responsible for all major manifestations of atherosclerosis on a cellular level. Previously we have shown that intracellular c...Accumulation of cholesterol in arterial cells, intracellular cholesterol retention, may be responsible for all major manifestations of atherosclerosis on a cellular level. Previously we have shown that intracellular cholesterol retention is the principal event in the genesis of atherosclerotic lesions. This allows us to consider cellular retention of cholesterol as a novel target for anti-atherosclerotic therapy. In this case the target is not the level of blood cholesterol but the level of cholesterol in vascular cells. This review describes our approach based on the use of cultured human arterial cells for the development of direct anti-atherosclerotic therapy. We use natural products as the basis of promising drugs for anti-atherosclerotic therapy. Using natural products, we have developed an approach to prevent intracellular cholesterol retention in cultured cells. Our knowledge of the mechanisms of atherosclerosis is the foundation on which we have developed drugs that have a direct anti-atherosclerotic effect, namely Allicor on the basis of garlic powder, anti-inflammatory drug Inflaminat (calendula, elder, and violet) possessing anti-cytokine activity and phytoestrogen-rich drug Karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid). Treatment with allicor or inflaminat has a direct anti-atherosclerotic effect on carotid atherosclerosis in asymptomatic men. Karinat prevents the development of carotid atherosclerosis in postmenopausal women. Thus, the main findings of our basic research have been successfully translated into clinical practice. As a result, this translation, a novel approach to the development of anti-atherosclerotic therapy, has been established. Our clinical trials have confirmed the suitability of innovative approach and the efficacy of novel drugs developed on the basis our methodology.展开更多
Connexins family in humans consists of 21 highly conserved proteins that are responsible for contact formation between cells. On the cell surface, connexins form hemichannels, or connexons. Two hemichannels brought to...Connexins family in humans consists of 21 highly conserved proteins that are responsible for contact formation between cells. On the cell surface, connexins form hemichannels, or connexons. Two hemichannels brought together form a gap junction, a form of intercellular contact that allows for direct transfer of material and signals between the adjacent cells. Gap junctions serve for transporting ions and other soluble, low molecular weight molecules therefore synchronizing the microenvironment of the contacting cells and maintaining cell and tissue homeostasis. Impairment of gap junctions is associated with different pathological conditions. Importantly, it has been described in atherosclerosis, which causes local cellular dysfunction in the arterial wall tissues followed by the development of atherosclerotic plaque. There are 3 main connexins expressed in human cardiovascular system: Cx37, Cx40, and Cx43. Alterations in the arterial wall cells observed in atherosclerosis include changes in the expression pattern of the main connexins and impairment of intercellular contacts and communication. According to the currently available data, Cx37 and Cx40 have anti-atherogenic and vasculoprotective properties, while Cx43 appears to be more pro-atherogenic. However, the effects of connexins are cell type-dependent and in many cases, remain to be studied in detail. In this review, we summarize the available knowledge on connexins of the arterial wall cells involved in atherosclerosis development.展开更多
文摘The key initiating process in atherogenesis is the subendothelial cholesterol retention, which is both necessary and sufficient to provoke lesion initiation. Retention of cholesterol transported by low density lipoprotien (LDL) in subendothelial cells of arterial wall, is an absolute requirement for lesion development. This allows us to consider intracellular cholesterol retention as a novel target for anti-atherosclerotic therapy. In this case, the target is not the level of blood cholesterol but the level of cholesterol in vascular cells. This review summarizes the results of our basic studies shedding light on the mechanisms of intracellular cholesterol retention. We describe our cellular models to search for anti-atherosclerotic agents and demonstrate the use of these models for the development of anti-atherosclerotic drugs. We use natural products as the basis of anti-atherosclerotic drugs because anti-atherosclerotic therapy should be long-term or even lifelong. Using cellular models and natural products, we have developed an approach to prevent intracellular cholesterol retention in cultured subendothelial aortic cells. We have developed drugs that reduce intracellular cholesterol retention, namely Allicor on the basis of garlic powder, anti-inflammatory drug Inflaminat (calendula, elder, and violet) possessing anti-cytokine activity and phytoestrogen-rich drug Karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid). Treatment with Allicor or Inflaminat caused regression of carotid atherosclerosis in asymptomatic men. Karinat prevented the development of new atherosclerotic plaques in postmenopausal women. Thus, the main findings of our basic research have been successfully translated into clinics. As a result, this translation, a novel approach to the development of anti-atherosclerotic therapy, has been established. Our clinical trials have confirmed the suitability of innovative approach and the efficacy of novel drugs developed on the basis our methodology.
文摘Accumulation of cholesterol in arterial cells, intracellular cholesterol retention, may be responsible for all major manifestations of atherosclerosis on a cellular level. Previously we have shown that intracellular cholesterol retention is the principal event in the genesis of atherosclerotic lesions. This allows us to consider cellular retention of cholesterol as a novel target for anti-atherosclerotic therapy. In this case the target is not the level of blood cholesterol but the level of cholesterol in vascular cells. This review describes our approach based on the use of cultured human arterial cells for the development of direct anti-atherosclerotic therapy. We use natural products as the basis of promising drugs for anti-atherosclerotic therapy. Using natural products, we have developed an approach to prevent intracellular cholesterol retention in cultured cells. Our knowledge of the mechanisms of atherosclerosis is the foundation on which we have developed drugs that have a direct anti-atherosclerotic effect, namely Allicor on the basis of garlic powder, anti-inflammatory drug Inflaminat (calendula, elder, and violet) possessing anti-cytokine activity and phytoestrogen-rich drug Karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid). Treatment with allicor or inflaminat has a direct anti-atherosclerotic effect on carotid atherosclerosis in asymptomatic men. Karinat prevents the development of carotid atherosclerosis in postmenopausal women. Thus, the main findings of our basic research have been successfully translated into clinical practice. As a result, this translation, a novel approach to the development of anti-atherosclerotic therapy, has been established. Our clinical trials have confirmed the suitability of innovative approach and the efficacy of novel drugs developed on the basis our methodology.
基金the Russian Science Foundation (Grant # 18-15-00254).
文摘Connexins family in humans consists of 21 highly conserved proteins that are responsible for contact formation between cells. On the cell surface, connexins form hemichannels, or connexons. Two hemichannels brought together form a gap junction, a form of intercellular contact that allows for direct transfer of material and signals between the adjacent cells. Gap junctions serve for transporting ions and other soluble, low molecular weight molecules therefore synchronizing the microenvironment of the contacting cells and maintaining cell and tissue homeostasis. Impairment of gap junctions is associated with different pathological conditions. Importantly, it has been described in atherosclerosis, which causes local cellular dysfunction in the arterial wall tissues followed by the development of atherosclerotic plaque. There are 3 main connexins expressed in human cardiovascular system: Cx37, Cx40, and Cx43. Alterations in the arterial wall cells observed in atherosclerosis include changes in the expression pattern of the main connexins and impairment of intercellular contacts and communication. According to the currently available data, Cx37 and Cx40 have anti-atherogenic and vasculoprotective properties, while Cx43 appears to be more pro-atherogenic. However, the effects of connexins are cell type-dependent and in many cases, remain to be studied in detail. In this review, we summarize the available knowledge on connexins of the arterial wall cells involved in atherosclerosis development.
