The assumption that upregulated Klotho protein in diseased hearts is derived from cleavage of the membrane-bound Klotho is further supported by our findings that (i) circulating sKlotho levels in serum were neither upregulated nor associated with disease progression in CHF and that (ii) full-length Klotho mRNA was upregulated in diseased hearts, whereas mRNA of secreted Klotho (isoform 2) was not detectable. Here, KL is linked to congestive heart failure.