Układ renina-angiotensyna-aldosteron w patogenezie miażdżycy. Wpływ na komórki śródbłonka i gromadzenie jednojądrzastych leukocytów w ścianie naczynia

Atherosclerosis is presently considered to be a type of chronic inflammatory disease in which development endothelial cell dysfunction, oxidative stress, and the fibroproliferative process within the vascular wall play very important role. Arterial hypertension, which is one of the major risk factors of atherosclerosis, may exert an important effect on many mechanisms significantly contributing to the development and progress of atherosclerosis. The article discusses in detail the role of endothelial cell dysfunction in atherosclerosis pathogenesis and mechanisms responsible for selective accumulation of mononuclear leukocytes within the vascular wall and thus for inflammation existing there. Subsequently, on the basis of the results of experimental and clinical studies, the possibilities of participation of hypertension, and in particular of angiotensin II, in these stages of development of atherosclerosis so significant for this disorder have been discussed. Morever, the article discusses how angiotensin II contributes to the intensity of inflammatory response and destabilisation of the atherosclerotic plaque and thus to the occurrence of clinical complication of atherosclerosis.Współcześnie uważa się, że miażdżyca jest rodzajemprzewlekłej choroby zapalnej, w przebiegu której istotną rolę odgrywa dysfunkcja komórek śródbłonka, stres oksydacyjny i toczący się w ścianie naczynia proces fibroproliferacyjny. Nadciśnienie tętnicze, będące jednym z głównych czynników ryzyka miażdżycy, może mieć istotny wpływ na wiele mechanizmów, które odgrywają istotną rolę w jej powstawaniu i progresji. W pracy szczegółowo omówiono rolę dysfunkcji komórek śródbłonka w patogenezie miażdżycy oraz mechanizmy odpowiedzialne za selektywne gromadzenie jednojądrzastych leukocytów w ścianie naczynia i tym samym rozwijające się tam zapalenie. Następnie na podstawie wyników badań eksperymentalnych i klinicznych przedyskutowano możliwości udziału nadciśnienia tętniczego, a szczególnie angiotensyny II, w poszczególnych etapach rozwoju miażdżycy. Ponadto omówiono sposób, w jaki angiotensyna II przyczynia się do nasilenia odpowiedzi zapalnej i destabilizacji blaszki miażdżycowej, co prowadzi do wystąpienia klinicznych powikłań miażdżycy

Lock, Stock and Barrel: Role of Renin-Angiotensin-Aldosterone System in Coronavirus Disease 2019

none16noSince the end of 2019, the medical-scientific community has been facing a terrible pandemic caused by a new airborne viral agent known as SARS-CoV2. Already in the early stages of the pandemic, following the discovery that the virus uses the ACE2 cell receptor as a molecular target to infect the cells of our body, it was hypothesized that the renin-angiotensin-aldosterone system was involved in the pathogenesis of the disease. Since then, numerous studies have been published on the subject, but the exact role of the renin-angiotensin-aldosterone system in the pathogenesis of COVID-19 is still a matter of debate. RAAS represents an important protagonist in the pathogenesis of COVID-19, providing the virus with the receptor of entry into host cells and determining its organotropism. Furthermore, following infection, the virus is able to cause an increase in plasma ACE2 activity, compromising the normal function of the RAAS. This dysfunction could contribute to the establishment of the thrombo-inflammatory state characteristic of severe forms of COVID-19. Drugs targeting RAAS represent promising therapeutic options for COVID-19 sufferers.openZanza, Christian; Tassi, Michele Fidel; Romenskaya, Tatsiana; Piccolella, Fabio; Abenavoli, Ludovico; Franceschi, Francesco; Piccioni, Andrea; Ojetti, Veronica; Saviano, Angela; Canonico, Barbara; Montanari, Mariele; Zamai, Loris; Artico, Marco; Robba, Chiara; Racca, Fabrizio; Longhitano, YaroslavaZanza, Christian; Tassi, Michele Fidel; Romenskaya, Tatsiana; Piccolella, Fabio; Abenavoli, Ludovico; Franceschi, Francesco; Piccioni, Andrea; Ojetti, Veronica; Saviano, Angela; Canonico, Barbara; Montanari, Mariele; Zamai, Loris; Artico, Marco; Robba, Chiara; Racca, Fabrizio; Longhitano, Yaroslav

Identification of a new population of TrkC+ sensory neurons that regulates blood pressure

Blood pressure is one of the vital signs and its regulation is crucial for survival. Several mechanisms contribute to maintain it in a physiological range: renin-angiotensin-aldosterone system, the autonomous nervous system and specialized baroreceptors neurons. In this study, we demonstrate the existence of a new population of sensory neurons marked by TrkC and TH that innervate blood vessels and are important in the control of blood pressure, blood flow and heart rate. Using an inducible Cre line driven from the TrkC locus, we show that TrkC is expressed in 30% of DRG neurons and that a fourth of these neurons are TH+ and project to blood vessels. Activation of TrkC+ TH+ neurons leads to high blood pressure, decreased blood flow and increased heart rate variability. Loss of function experiments revealed that TrkC+ TH+ sensory neurons are crucial for life. Ablation of TrkC+ neurons results in low blood pressure, alteration of blood flow and increased heart rate variability. All these cardiovascular alterations lead ablate mice to death within 48 hours. We also demonstrate that TrkC+ neurons do not act directly on blood vessels, but they exert their functions through a circuit with the sympathetic nervous system. We thus identified a new population of sensory neurons involved in the regulation of blood pressure, blood flow and heart rate and we hope that this can lead to the development of new therapeutic strategies in the near future