angiotensin-i and Thrombosis

In human pathology, SARS-CoV-2 utilizes multiple molecular pathways to determine structural and biochemical changes within the different organs and cell types. The clinical picture of patients with COVID-19 is characterized by a very large spectrum. The reason for this variability has not been clarified yet, causing the inability to make a prognosis on the evolution of the disease.. PubMed search was performed focusing on the role of ACE 2 receptors in allowing the viral entry into cells, the role of ACE 2 downregulation in triggering the tissue pathology or in accelerating previous disease states, the role of increased levels of Angiotensin II in determining endothelial dysfunction and the enhanced vascular permeability, the role of the dysregulation of the renin angiotensin system in COVID-19 and the role of cytokine storm.. The pathological changes induced by SARS-CoV-2 infection in the different organs, the correlations between the single cell types targeted by the virus in the different human organs and the clinical consequences, COVID-19 chronic pathologies in liver fibrosis, cardiac fibrosis and atrial arrhythmias, glomerulosclerosis and pulmonary fibrosis, due to the systemic fibroblast activation induced by angiotensin II are discussed.. The main pathways involved showed different pathological changes in multiple tissues and the different clinical presentations. Even if ACE2 is the main receptor of SARS-CoV-2 and the main entry point into cells for the virus, ACE2 expression does not always explain the observed marked inter-individual variability in clinical presentation and outcome, evidencing the complexity of this disorder. The proper interpretation of the growing data available might allow to better classifying COVID-19 in human pathology.

Topics: Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme 2; Atrial Fibrillation; Blood Coagulation; Capillary Permeability; Cardiomyopathies; COVID-19; Cytokine Release Syndrome; Cytokines; Endothelium, Vascular; Fibroblasts; Fibrosis; Humans; Liver Cirrhosis; Myocarditis; Receptors, Coronavirus; Renin-Angiotensin System; SARS-CoV-2; Systemic Inflammatory Response Syndrome; Thrombosis; Virus Internalization

Type 2 diabetes mellitus (T2DM) is an increasing problem in childhood; however type 1 diabetes mellitus (T1DM) remains by far the most common type of diabetes in this age group. In this review we will focus on T1DM, because this will have the greatest implication for patients diagnosed in childhood. During the atherosclerotic process, several molecular, receptorial and cellular factors provide a continous mechanism of vascular damage. In diabetic children this state seems to be enhanced and facilitated so that accelerated atherosclerosis is associated with an increased risk of cardiovascular events in respect to the non diabetic population. Hyperglycemia PER SE and associated with diabetes is an important risk factor for atherosclerosis. At present a substantial part of children with diabetes do not reach satisfactory glycemic control. Other risk factors for the development and progression of atherosclerosis may be inherited or develop in the course of the disease: hypertension, dyslipidemia, insulin resistance, obesity, cigarette smoking, physical inactivity, disturbance of platelet function, coagulation and fibrinolysis. The development and progression of atherosclerosis should be blocked at an early age, if possible. Primary prevention to all risk factors for cardiovascular disease is important and intervention is indicated if necessary. At the moment the best therapeutic strategy is to maintain metabolic control at a physiologic level and perform screening and early intervention for vascular complications.

Topics: Adult; Angiotensin I; Angiotensin II; Atherosclerosis; Child; Cholesterol, LDL; Diabetic Angiopathies; Fatty Liver; Humans; Inflammation; Macrophages; Thrombosis

Angiotensin-(1-7) [Ang-(1-7)] is an active member of renin-angiotensin system (RAS). It counterbalances vasoconstriction, mitogenic, arrhythmogenic and prothrombotic actions of Ang II. Inducing natiuresis and diuresis opposes also the water and sodium retention produced by Ang II. Till now the specific receptor side for Ang-(1-7) has been not cloned, but the current data strongly suggest that an interaction (cross-talk) between angiotensin receptors may play a role in the effects of Ang-(1-7).

Topics: Angiotensin I; Animals; Cardiovascular Physiological Phenomena; Cell Division; Humans; Kidney; Peptide Fragments; Receptors, Angiotensin; Renin-Angiotensin System; Thrombosis

In vitro and in vivo data provide compelling evidence for an interaction between the RAS and thrombosis. Furthermore, angiotensin and AT1 receptor blockers may influence platelet function. ACE is strategically poised to regulate these interactions. ACE catalyzes the conversion of Ang I to Ang II, which in turn stimulates the production of PAI-1, sensitizes platelets, promotes the production of superoxide radicals that scavenge free NO, and induces the expression of tissue factor. Conversely, ACE catalyzes the breakdown of bradykinin, a potent stimulus to t-PA secretion. These data suggest that clinical, genetic, or environmental factors (such as salt intake and medications) that alter ACE activity and Ang II production would be expected to impact on clotting and fibrinolytic mechanisms.

Topics: Angiotensin I; Angiotensin II; Angiotensin Receptor Antagonists; Angiotensins; Blood Coagulation; Blood Platelets; Bradykinin; Fibrinolysis; Fibrinolytic Agents; Free Radical Scavengers; Humans; Nitric Oxide; Peptidyl-Dipeptidase A; Plasminogen Activator Inhibitor 1; Renin-Angiotensin System; Serine Proteinase Inhibitors; Superoxides; Thrombosis; Tissue Plasminogen Activator

Bradykinin B2 receptor-deleted mice (Bdkrb2(-/-)) have delayed carotid artery thrombosis times and prolonged tail bleeding time resulting from elevated angiotensin II (AngII) and angiotensin receptor 2 (AT2R) producing increased plasma nitric oxide (NO) and prostacyclin. Bdkrb2(-/-) also have elevated plasma angiotensin-(1-7) and messenger RNA and protein for its receptor Mas. Blockade of Mas with its antagonist A-779 in Bdkrb2(-/-) shortens thrombosis times (58 ± 4 minutes to 38 ± 4 minutes) and bleeding times (170 ± 13 seconds to 88 ± 8 seconds) and lowers plasma nitrate (22 ± 4 μM to 15 ± 5 μM), and 6-keto-PGF1α (259 ± 103 pg/mL to 132 ± 58 pg/mL). Bdkrb2(-/-) platelets express increased NO, guanosine 3',5'-cyclic monophosphate, and cyclic adenosine monophosphate with reduced spreading on collagen, collagen peptide GFOGER, or fibrinogen. In vivo A-779 or combined L-NAME and nimesulide treatment corrects it. Bdkrb2(-/-) platelets have reduced collagen-related peptide-induced integrin α2bβ3 activation and P-selectin expression that are partially corrected by in vivo A-779, nimesulide, or L-NAME. Bone marrow transplantations show that the platelet phenotype and thrombosis time depends on the host rather than donor bone marrow progenitors. Transplantation of wild-type bone marrow into Bdkrb2(-/-) hosts produces platelets with a spreading defect and delayed thrombosis times. In Bdkrb2(-/-), combined AT2R and Mas overexpression produce elevated plasma prostacyclin and NO leading to acquired platelet function defects and thrombosis delay.

Topics: Angiotensin I; Angiotensin II; Animals; Bleeding Time; Blood Platelets; Bone Marrow Transplantation; Cyclic AMP; Cyclic GMP; Epoprostenol; Immunoblotting; Mice; Mice, 129 Strain; Mice, Knockout; NG-Nitroarginine Methyl Ester; Nitric Oxide; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Membrane Glycoproteins; Proto-Oncogene Mas; Proto-Oncogene Proteins; Receptor, Angiotensin, Type 2; Receptor, Bradykinin B2; Receptors, G-Protein-Coupled; Reverse Transcriptase Polymerase Chain Reaction; Sulfonamides; Thrombosis; Time Factors

Angiotensin (Ang) (1-9) is the renin-angiotensin-system peptide found in the plasma of healthy volunteers and after angiotensin-converting-enzyme inhibitors therapy. In vitro experiments proved that Ang-(1-9) may be produced from Ang I. In our study, we tried to expand the poor data about the in vivo properties of Ang-(1-9). We revealed that Ang-(1-9) enhanced electrically stimulated arterial thrombosis in the carotid artery of Wistar rats. Losartan, a selective blocker of AT1 receptor for Ang II, abolished the prothrombotic activity of Ang-(1-9). This peptide increased plasma level of fibrinogen, augments fibrin generation, and similarly to Ang II, potentiated collagen induced platelet aggregation. Using HPLC, we found that after incubation of Ang-(1-9) with platelet homogenates or after intravenous administration this peptide is converted to Ang II. We concluded that Ang-(1-9) exerts an Ang II-like prothrombotic effect due to the conversion to Ang II in the circulatory system of rats and that platelets are involved in this process.

Topics: Angiotensin I; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Animals; Arteries; Blood Platelets; Humans; Losartan; Male; Partial Thromboplastin Time; Peptide Fragments; Platelet Aggregation; Prothrombin Time; Rats; Rats, Wistar; Thrombosis

To investigate whether diabetic retinopathy (DR) is associated with abnormalities in: (i) aqueous humour Angiotensin I (Ang I) and Angiotensin II (Ang II) levels; and (ii) plasma Ang I, soluble P-selectin, lipoprotein (a) (Lp(a)), endothelial markers and haemorheological abnormalities.. Cross-sectional study of diabetic patients and healthy controls undergoing cataract surgery.. 21 diabetic patients (12 males; mean age 67.0 years) were studied. Plasma levels of Ang II were lower in diabetics compared with controls (p<0.05). There were no differences in mean aqueous Ang I and Ang II levels in diabetics with or without proliferative DR compared with controls. Mean systolic blood pressure was higher in Group 1 patients (p=0.02). Patients with DR also demonstrated high Lp (a) and abnormal haemorheological factors (fibrinogen, white cell count).. Ang I and Ang II do not significantly contribute to the pathogenesis of DR. Patients with DR also had abnormal Lp (a) and haemorheological factors. The role of hypertension in the pathogenesis of DR needs further evaluation.

Topics: Aged; Angiotensin I; Angiotensin II; Aqueous Humor; Blood Pressure; Cell Division; Cross-Sectional Studies; Diabetic Retinopathy; Endothelium, Vascular; Female; Hemorheology; Humans; Lipoprotein(a); Male; Neovascularization, Pathologic; P-Selectin; Retinal Neovascularization; Retinal Vessels; Thrombosis