Capsaicin-sensitive sensory neurons regulate myocardial function and gene expression pattern of rat hearts: a DNA microarray study.
We have previously shown that capsaicin-sensitive sensory nerves contribute to the regulation of normal cardiac function and to the development of cardiac adaptation to ischemic stress; however, the underlying molecular mechanisms remain unknown. Therefore, here we assessed cardiac functional alterations and relative gene expression changes by DNA microarray analysis of 6400 genes in rat hearts 7 days after the end of systemic capsaicin treatment protocol leading to selective sensory chemodenervation. Capsaicin pretreatment resulted in a cardiac dysfunction characterized by elevation of left ventricular end-diastolic pressure and led to altered expression of 80 genes of known function or homology to known sequences. Forty-seven genes exhibited significant up-regulation and 33 genes were down-regulated (changes ranged from -3.9 to +4.8-fold). The expression changes of 10 selected genes were verified, and an additional 11 genes were examined by real-time quantitative PCR. This is the first demonstration that gene expression changes in the heart due to capsaicin pretreatment included vanilloid receptor-1 (capsaicin receptor), transient receptor potential protein, GABA receptor rho-3 subunit, 5-hydroxytryptamine 3 receptor B, neurokinin receptor 2, endothelial nitric oxide synthase, matrix metalloproteinase-13, cytochrome P450, farnesyl-transferase, ApoB, and leptin. None of the genes have been previously shown to be involved in the mechanism of the cardiac functional effects of sensory chemodenervation by capsaicin. We conclude that capsaicin-sensitive sensory nerves play a significant role in the regulation of a variety of neuronal and non-neuronal genes in the heart and possibly in other tissues as well.
Zvara
Agnes
A
Laboratory of Functional Genomics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary.
Bencsik
Péter
P
Fodor
Gabriella
G
Csont
Tamás
T
Hackler
László
L
Dux
Mária
M
Fürst
Susanna
S
Jancsó
Gábor
G
Puskás
László G
LG
Ferdinandy
Péter
P
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006321:Heart / Q000294:innervation* / Q000502:physiology*; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017208:Rats, Wistar; D050916:TRPV Cation Channels / Q000378:metabolism
D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin