RESUMO
Collateral blood flow is a natural way of compensation of blood supply of ischemic myocardium however its efficacy is highly individual. Revelation of potentially modifiable factors acting on which it would be possible to change the state of collateral blood flow will allow to find an approach to improvement of prognosis and quality of life of patients with ischemic heart disease. In this review we show significance of collateral blood flow, analyze mechanisms of its formation, and stress the role of vascular endothelial growth factor-A (VEGF-A) and its genetic polymorphism.
Assuntos
Vasos Coronários , Isquemia Miocárdica , Fator A de Crescimento do Endotélio Vascular/genética , Circulação Colateral , Circulação Coronária , Vasos Coronários/metabolismo , Vasos Coronários/fisiopatologia , Humanos , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , Miocárdio/metabolismo , Polimorfismo Genético , PrognósticoRESUMO
The role of various inflammatory mechanisms and oxidative stress in the development of atherosclerosis and arterial hypertension (AH) has been increasingly acknowledged during recent years. Hypertension per se or factors that cause hypertension along with other complications lead to infiltration of activated leukocytes in the vascular wall, where these cells contribute to the development of vascular injury by releasing cytokines, oxygen radicals, and other toxic mediators. However, molecular mechanisms underlying leukocyte activation at transcriptional level in AH are still far from being clear. To solve this problem we employed cDNA microarray technology to reveal the differences in gene expression in peripheral blood leukocytes from patients with AH compared with healthy individuals. The microarray data were verified by a semi-quantitative RT-PCR method. We found 25 genes with differential expression in leukocytes from AH patients among which 21 genes were upregulated and 4 genes were downregulated. These genes are implicated in apoptosis (CASP2, CASP4, and CASP8, p53, UBID4, NAT1, and Fte-1), inflammatory response (CAGC, CXCR4, and CX3CR1), control of MAP kinase function (PYST1, PAC1, RAF1, and RAFB1), vesicular trafficking of molecules among cellular organelles (GDI-1 and GDI-2), cell redox homeostasis (GLRX), cellular stress (HSPA8 and HSP40), and other processes. Gene expression pattern of the majority of genes was similar in AH patients independent of the disease stage and used hypotensive therapy, but was clearly different from that of normotensive subjects.
Assuntos
Perfilação da Expressão Gênica , Regulação da Expressão Gênica/fisiologia , Hipertensão/genética , Hipertensão/metabolismo , Leucócitos/metabolismo , Adulto , Idoso , Feminino , Humanos , Hipertensão/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de OligonucleotídeosRESUMO
Hypertrophy of left ventricular myocardium observed in 15-20% of patients with arterial hypertension is an independent factor which elevates considerably risk of complications of hypertension (ischemic heart disease, chronic heart failure, ventricular arrhythmias). Regression of left ventricular hypertrophy (LVH) at the background of hypotensive therapy is associated with additional lowering of cardiovascular risk. This should be taken into consideration in selection of a hypotensive preparation. Angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) are believed to have most pronounced ability to cause reverse development of LVH. It has been shown in recently finished PIXEL trial that administration of fixed combination of ACEI perindopril and diuretic indapamide reduced LVH more effectively than monotherapy with high doses of ACEI enalapril and provided better blood pressure control. Therefore in a patient with hypertension and LVH it is expedient to consider combined therapy with ACEI and diuretic including use of their fixed combinations as treatment of choice.
Assuntos
Hipertrofia Ventricular Esquerda/fisiopatologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Diuréticos/uso terapêutico , Quimioterapia Combinada , Humanos , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Indapamida/uso terapêutico , Perindopril/uso terapêutico , Fatores de RiscoRESUMO
The review summarizes data obtained by the authors and other laboratories concerning the role of urokinase plasminogen activator in vessel remodeling and angiogenesis. The data have shown that urokinase is involved in unfavorable vascular remodeling during the development of restenosis, atherosclerosis and also in the regulation of angiogenesis. Urokinase is a promising target for therapeutic interventions aimed at restenosis prevention. Urokinase gene therapy may be a perspective strategy for the treatment of tissue ischemia.