minocycline and Aortic-Valve-Stenosis

Ochronosis refers to the blue-black discoloration of connective tissue. While cardiovascular ochronosis has been described resulting from alkaptonuria, it may also result from chronic minocycline use which is exceedingly rare. Cardiovascular ochronosis often presents with insidious development, often identified incidentally during aortic valve replacement (AVR). Herein, we describe the case of a 71-year-old male undergoing AVR and coronary artery bypass grafting found to have minocycline-induced ochronosis of the aortic valve and aorta.. Given the rarity of this case, descriptions of cardiovascular ochronosis cases secondary to minocycline use are imperative in ensuring that it is on the differential diagnosis when identified by others in future cases. Additional care must be taken intraoperatively to ensure that the correct anatomy is identified as discoloration hinders visualization of the anatomy potentially resulting in unintentional consequences such as heart block or perivalvular leak as traditional visual cues for suture placement are distorted.

Topics: Aged; Alkaptonuria; Aorta; Aortic Valve; Aortic Valve Stenosis; Heart Valve Prosthesis Implantation; Humans; Male; Minocycline; Ochronosis

Minocycline, a derivative of tetracycline, is a broad-spectrum antibiotic used in the treatment of various infections. Black discolouration of the skin, teeth, bones and the thyroid gland are sequelae of long-term minocycline therapy. We report an unusual case of minocycline-induced pigmentation of the aortic valve and sinuses of Valsalva.

Topics: Aged; Anti-Bacterial Agents; Aortic Diseases; Aortic Valve; Aortic Valve Stenosis; Biopsy; Drug Administration Schedule; Female; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hidradenitis; Humans; Minocycline; Pigmentation; Pigmentation Disorders; Sinus of Valsalva

Minocycline, a tetracycline derivate, mediates vasculoprotective effects independent of its antimicrobial properties. Thus, minocycline protects against diabetic nephropathy and reduces neointima formation following vascular injury through inhibition of apoptosis or migration, respectively. Whether minocycline has an effect on primary atherogenesis remains unknown.. Using morphological and immunohistochemical analyses we determined de novo atherogenesis in ApoE-/- mice receiving a high fat diet (HFD) with or without minocycline treatment. The effect of minocycline on proliferation, expression of p27(Kip1) or PARP-1 (Poly [ADP-ribose] polymerase 1), or on PAR (poly ADP-ribosylation) modification in vascular smooth muscle cells (VSMC) was analyzed in ex vivo and in vitro (primary human and mouse VSMC).. Minocycline reduced plaque size and stenosis in ApoE-/- HFD mice. This was associated with a lower number and less proliferation of VSMC, reduced PAR (poly ADP-ribosylation) modification and increased p27(Kip1) expression within the plaques. In agreement with the ex vivo data minocycline reduced proliferation, PARP-1 expression, PAR modification while inducing p27 expression in human and mouse VSMC in vitro. These effects were observed at a low minocycline concentration (10 μM), which had no effect on VSMC migration or apoptosis. Minocycline inhibited PARP-1 and induced p27(Kip1) expression in VSMC as efficiently as the specific PARP-1 inhibitor PJ 34. Knock down of p27(Kip1) abolished the antiproliferative effect of minocycline. These data establish a novel antiatherosclerotic mechanism of minocycline during de novo atherogenesis, which depends on p27(Kip1) mediated inhibition of VSMC proliferation.

Topics: Animals; Aortic Valve Stenosis; Apolipoproteins E; Atherosclerosis; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p27; Diet, High-Fat; Humans; Mice; Minocycline; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Phenanthrenes; Plaque, Atherosclerotic; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases