The SHR is the most widely studied animal model of hypertension. In this strain, as in many humans with essential hypertension, increased blood pressure has been reported to cluster with other risk factors for cardiovascular disease, including insulin resistance and dyslipidemia. However, the genetic mechanisms that mediate this clustering of risk factors for cardiovascular disease or the hypertension "metabolic syndrome" remain poorly understood. In the current studies, we have demonstrated (1) that a gene or genes responsible for a whole spectrum of cardiovascular risk factors mapped to a limited segment of the centromeric region of rat chromosome 4, (2) that a spontaneous deletion in the gene for Cd36 that encodes a fatty acid transporter and is located directly at the peak of QTL linkages on chromosome 4 has been indirectly linked to the transmission of insulin resistance, defective fatty acid metabolism, and increased blood pressure, and (3) based on complementation analysis in two transgenic lines expressing wild-type Cd36 on the genetic background of the SHR strain harboring the deletion variant of Cd36, we have established that defective Cd36 can be a determinant of disordered fatty acid metabolism, glucose intolerance, and insulin resistance in spontaneous hypertension.

• MeSH
• antigeny CD36 genetika   fyziologie   MeSH
• delece genu MeSH
• dietní sacharidy farmakokinetika   MeSH
• dietní tuky farmakokinetika   MeSH
• genetická vazba MeSH
• geneticky modifikovaná zvířata MeSH
• hyperlipidemie epidemiologie   genetika   MeSH
• hypertenze epidemiologie   genetika   MeSH
• inzulinová rezistence genetika   MeSH
• komplementární DNA genetika   MeSH
• krevní tlak genetika   MeSH
• krysa rodu Rattus MeSH
• kvantitativní znak dědičný MeSH
• ledviny patofyziologie   MeSH
• lidé MeSH
• lipolýza genetika   MeSH
• mapování chromozomů MeSH
• mastné kyseliny metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• mutace MeSH
• myši knockoutované MeSH
• myši MeSH
• potkani inbrední SHR genetika   MeSH
• rizikové faktory MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• sekvenční delece MeSH
• testy genetické komplementace MeSH
• translokace genetická genetika   MeSH
• zvířata kongenní MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antigeny CD36 MeSH
• dietní sacharidy MeSH
• dietní tuky MeSH
• komplementární DNA MeSH
• mastné kyseliny MeSH

Disorders of carbohydrate and lipid metabolism have been reported to cluster in patients with essential hypertension and in spontaneously hypertensive rats (SHRs). A deletion in the Cd36 gene on chromosome 4 has recently been implicated in defective carbohydrate and lipid metabolism in isolated adipocytes from SHRs. However, the role of Cd36 and chromosome 4 in the control of blood pressure and systemic cardiovascular risk factors in SHRs is unknown. In the SHR. BN-Il6/Npy congenic strain, we have found that transfer of a segment of chromosome 4 (including Cd36) from the Brown Norway (BN) rat onto the SHR background induces reductions in blood pressure and ameliorates dietary-induced glucose intolerance, hyperinsulinemia, and hypertriglyceridemia. These results demonstrate that a single chromosome region can influence a broad spectrum of cardiovascular risk factors involved in the hypertension metabolic syndrome. However, analysis of Cd36 genotypes in the SHR and stroke-prone SHR strains indicates that the deletion variant of Cd36 was not critical to the initial selection for hypertension in the SHR model. Thus, the ability of chromosome 4 to influence multiple cardiovascular risk factors, including hypertension, may depend on linkage of Cd36 to other genes trapped within the differential segment of the SHR. BN-Il6/Npy strain.

• MeSH
• antigeny CD36 genetika   MeSH
• cerebrovaskulární poruchy genetika   patofyziologie   MeSH
• fenotyp MeSH
• genotyp MeSH
• hemodynamika genetika   MeSH
• hypertenze genetika   patofyziologie   MeSH
• inzulin krev   genetika   MeSH
• krevní glukóza genetika   metabolismus   MeSH
• krysa rodu Rattus MeSH
• lipidy krev   genetika   MeSH
• potkani inbrední BN MeSH
• potkani inbrední SHR MeSH
• rizikové faktory MeSH
• sekvenční delece MeSH
• shluková analýza MeSH
• zvířata kongenní MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Názvy látek
• antigeny CD36 MeSH
• inzulin MeSH
• krevní glukóza MeSH
• lipidy MeSH

Abnormalities in carbohydrate and lipid metabolism are common in patients with essential hypertension and in the spontaneously hypertensive rat (SHR). To identify chromosome regions contributing to this clustering of cardiovascular risk factors in the SHR, we searched for quantitative trait loci (QTL) associated with insulin resistance, glucose intolerance, and dyslipidemia by using the HXB/BXH recombinant inbred (RI) strains. Analysis of variance in RI strains suggested significant effects of genetic factors. A genome screening of the RI strains with more than 700 markers revealed QTL significantly associated with insulin resistance on Chromosomes (Chrs) 3 and 19. The Chr 19 QTL was confirmed by testing a previously derived SHR-19 congenic strain: transfer of a Chr 19 segment delineated by markers D19Rat57 and D19Mit7 from the Brown Norway (BN/Cr) strain onto the genetic background of the SHR/Ola was associated with decreased insulin and glucose concentrations and ameliorated insulin resistance at the tissue level. These findings suggest that closely linked genes on Chr 19, or perhaps even a single gene with pleiotropic effects, influence the clustering of metabolic disturbances in the SHR-BN model.

• MeSH
• cholesterol krev   metabolismus   MeSH
• glukosa analýza   metabolismus   MeSH
• glukózový toleranční test MeSH
• hyperlipidemie genetika   MeSH
• inzulin krev   metabolismus   MeSH
• inzulinová rezistence genetika   MeSH
• krysa rodu Rattus MeSH
• kvantitativní znak dědičný * MeSH
• modely nemocí na zvířatech MeSH
• porucha glukózové tolerance genetika   MeSH
• potkani inbrední BN MeSH
• potkani inbrední SHR genetika   metabolismus   MeSH
• triglyceridy krev   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Názvy látek
• cholesterol MeSH
• glukosa MeSH
• inzulin MeSH
• triglyceridy MeSH