Atherosclerosis

From Dog
Macroscopic view of the left ventricle of the heart, showing pronounced atherosclerotic changes (arrows)[1]
Brain of a 2-year-old Australia Shepherd which died from acute neurological signs secondary to hypothyroidism, showing severe atherosclerosis of the brain and spinal cord[2]

Atherosclerosis (hardening of the arteries) is a cardiovascular and fibroproliferative inflammatory disease commonly associated with age- and dietary-related factors in humans, but is relatively rare in dogs.

A breed predisposition has been reported in the Miniature Schnauzer[3], Doberman Pinscher, Labrador Retriever and Portuguese Water Dog[4].

In dogs, which have markedly shorter life spans compared to humans, atherosclerosis does occur but usually secondary to chronic inflammatory diseases such as periodontitis[4], hypothyroidism[5], diabetes mellitus[6], hyperlipidemia[7], hypercholesterolemia[8] and dyspnea associated with obesity[9] or brachycephalic syndrome.

The disease usually occurs systemically, affecting the brain, spinal cord, heart, spleen, kidneys, lungs, pancreas, alimentary tract, urogenital organs, eyes, prostate and urinary bladder[10].

Hyperadrenocorticism does not appear to significantly increase risks of atherosclerosis formation in dogs[11].

Originally thought to develop as an 'inside-out' process, where atheromas form in the intima and work their way outward into the adventitia, atherosclerosis in now considered to develop in an 'outside-in' fashion, where vessel wall inflammation begins in the adventitia and works its way into the media and intima[12]. Regardless, atherosclerosis is characterized by thickening of the tunica media/interna of arterial walls, associated with lipid deposition. Smooth muscle and lipid-filled macrophages known as foam cells proliferate in the tunica media/interna, and a fibrous plaque forms around a core of lipid (atheroma)[11].

In dogs, advanced glycation end products appear critical to atheroma formation[13]. These adhesive glycoprotein normally support hemostasis by mediating platelet adhesion to injured vessel surfaces and are implicated as critical in atheroma formation. In dogs with von Willebrand's disease, atherosclerosis has been shown not to occur[14], implicating adhesive glycoproteins in the development of canine atherosclerosis.

There are numerous reports linking an association between Helicobacter pylori and Chlamydophila psittaci infection and human coronary atherosclerosis, but these infectious agents do not appear to be incriminated in atherosclerosis in dogs[1][15].

The primary complications of atherosclerosis are thromboembolism, increased risk of cataract formation (due to hyperlipidemia)[16] and central and/or peripheral neuropathology. Thromboembolism, which can trigger rupture or damage of lipid-rich coronary plaques, is less common in dogs compared with humans.

The most significant consequence of atherosclerosis is peripheral and/or central nervous ischemia and compression caused by myxedematous deposits[17]. This invariably leads to peripheral polyneuropathy and/or central cognitive deficit syndrome[18].

Dogs that develop atherosclerosis have increased lipoprotein levels, primarily in the β and α2 low density lipoproteins, which predisposes to increased microvascular ischemia and blood viscosity, putting dogs at risk of thromboembolic episodes[9].

Correction of underlying inflammatory diseases and use of statins may ameliorate clinical signs, and nutritional supplements may assist management of this condition[19].

The use of antioxidants (vitamins E and C, fruits and vegetables) and mitochondrial cofactors (e.g. Co-Q10, S-adenosylmethionine[20], lipoic acid and carnitine)[21] have been shown to significantly improve cognitive function in aged dogs[22].

References

  1. 1.0 1.1 Sostaric-Zuckermann IC et al (2011) Chlamydia in canine or feline coronary arteriosclerotic lesions. BMC Res Notes 4:350
  2. Blois SL et al (2008) A case of primary hypothyroidism causing central nervous system atherosclerosis in a dog. Can Vet J 49(8):789-792
  3. Wong VM et al (2011) Serum C-reactive protein concentrations in healthy Miniature Schnauzer dogs. Vet Clin Pathol 40(3):380-383
  4. 4.0 4.1 Chase K et al (2011) Age relationships of postmortem observations in Portuguese Water Dogs. Age (Dordr) 33(3):461-73
  5. Indrieri R et al (1987) Neuromuscular abnormalities associated with hypothyroidism and lymphocytic thyroiditis in three dogs. J Am Vet Med Assoc 190(5):544-548
  6. Bennett N (2002) Monitoring techniques for diabetes mellitus in the dog and the cat. Clin Tech Small Anim Pract 17(2):65-69
  7. Xenoulis PG & Steiner JM (2010) Lipid metabolism and hyperlipidemia in dogs. Vet J 183(1):12-21
  8. Garosi L (2005) Ischaemic stroke stroke in dogs and humans: a comparative review. J Small Anim Pract 46:521-529
  9. 9.0 9.1 Liu SK et al (1986) Clinical and pathologic findings in dogs with atherosclerosis: 21 cases (1970-1983). J Am Vet Med Assoc 189(2):227-232
  10. Kagawa Y et al (1998) Systemic atherosclerosis in dogs: histopathological and immunohistochemical studies of atherosclerotic lesions. J Comp Pathol 118(3):195-206
  11. 11.0 11.1 Hess RS (2003) Association between diabetes mellitus, hypothyroidism or hyperadrenocorticsm and atherosclerosis in dogs. J Vet Intern Med 17:489-494
  12. Galkina E & Ley K (2009) Immune and inflammatory mechanisms of atherosclerosis. Annu Rev Immunol 27:165–197
  13. Chiers K et al (2010) Accumulation of advanced glycation end products in canine atherosclerosis. J Comp Pathol 143(1):65-69
  14. Nichols TC et al (1993) The roles of von Willebrand factor and factor VIII in arterial thrombosis: studies in canine von Willebrand disease and hemophilia A. Blood 81(10):2644–2651
  15. Sako T et al (2002) Chlamydial infection in canine atherosclerotic lesions. Atherosclerosis 162(2):253-259
  16. Sottiaux J et al (1999) Atherosclerosis in a dog with diabetes mellitus. J Small Anim Pract 40(12):581-584
  17. Jaggy A (1994) Neurological manifestations of hypothyroidism: a retrospective study of 29 dogs. J Vet Intern Med 8(5):328-336
  18. Vitale C (2007) Neurologic dysfunction in hypothyroid, hyperlipidemic Labrador retrievers. J Vet Intern Med 21:1316-1322
  19. Laflamme DP (2012) Nutritional care for aging cats and dogs. Vet Clin North Am Small Anim Pract 42(4):769-791
  20. Rème CA et al (2008) Effect of S-adenosylmethionine tablets on the reduction of age-related mental decline in dogs: a double-blinded, placebo-controlled trial. Vet Ther 9(2):69-82
  21. Head E et al (2009) Effects of age, dietary, and behavioral enrichment on brain mitochondria in a canine model of human aging. Exp Neurol 220(1):171-176
  22. Manteca X et al (2011) Nutrition and behavior in senior dogs. Top Companion Anim Med 26(1):33-36