Abstract
Hypertension is a hemodynamic disorder and one of the most important and well-established risk factors for vascular diseases such as stroke. Blood vessels exposed to chronic shear stress develop structural changes and remodeling of the vascular wall through many complex mechanisms. However, the molecular mechanisms involved are not fully understood. Hypertension-susceptible genes may provide a novel insight into potential molecular mechanisms of hypertension and secondary complications associated with hypertension. The aim of this exploratory study was to identify gene expression differences in the middle cerebral arteries between 12-week-old male spontaneously hypertensive rats and their normotensive Wistar-Kyoto rats using an Affymetrix whole-transcriptome expression profiling. Quantitative PCR and western blotting were used to verify genes of interest. 169 genes were differentially expressed in the middle cerebral arteries from hypertensive compared to normotensive rats. The gene expression of 72 genes was decreased and the gene expression of 97 genes was increased. The following genes with a fold difference ≥1.40 were verified by quantitative PCR; Postn, Olr1, Fas, Vldlr, Mmp2, Timp1, Serpine1, Mmp11, Cd34, Ptgs1 and Ptgs2. The gene expression of Postn, Olr1, Fas, Vldlr, Mmp2, Timp1 and Serpine1 and the protein expression of LOX1 (also known as OLR1) were significantly increased in the middle cerebral arteries from spontaneously hypertensive rats compared to Wistar-Kyoto rats. In conclusion, the identified genes in the middle cerebral arteries from spontaneously hypertensive rats could be possible mediators of the vascular changes and secondary complications associated with hypertension. This study supports the selection of key genes to investigate in the future research of hypertension-induced end-organ damage.
Highlights
Hypertension is a hemodynamic disorder and one of the most important and well-established risk factors for cardiovascular diseases and stroke
Out of 169 genes, the expression of 72 genes was decreased and the expression of 97 genes was increased in middle cerebral arteries (MCAs) from spontaneously hypertensive rats (SHRs) compared to WKY rats
Biological process was further subdivided into one Gene ontology (GO) term named positive regulation of gene expression, and cellular component was further subdivided into three GO terms named extracellular region, extracellular matrix and extracellular space (Fig 1)
Summary
Hypertension is a hemodynamic disorder and one of the most important and well-established risk factors for cardiovascular diseases and stroke. Essential hypertension is defined as blood pressure of 140/90 mmHg or above of unknown cause [1]. The blood pressure is not controlled in nearly 50% of hypertensive patients due to no obvious symptoms of essential hypertension [2,3]. The consequence is a large group of patients in high risk of secondary complications.
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