Mechanotransduction and the Myogenic Response in Diabetes - The Mechanobiology of Obesity and Related Diseases - page 253

between VSMCs and ECM proteins, it is tempting to speculate a link between
diabetes-induced changes in the ECM (including alterations in synthesis, cross-
linking and glycation) and mechanosensation. Further, alterations at the level of
ion channels, second messengers and the contractile proteins provide alternate
mechanisms for diabetes-induced impairment in myogenic signaling. Interpreta-
tion of data from experimental animal studies is further complicated from
a number of factors in experimental design. Thus, many studies have been per-
formed on a variety of rodent models, typically restricted to male animals and
without direct consideration of duration of diabetes. Similarly, in human studies,
as diabetes is a multi-factorial disease, there is a need to consider other metabolic
disorders including hypertension, hypercholesterolemia, dyslipidemia and obesity.
Importantly, each of these disorders has been shown to impact mechanotrans-
duction-related signaling pathways. Common to studies of both human subjects
and animal models is the impact of vascular heterogeneity. Understanding of
tissue-specific differences in mechanical signaling does, however, provide poten-
tial to the rationale for targeted therapeutic interventions.

Acknowledgments Aspects of work presented in this chapter were supported by NIH grants
(HL085119 and HL092241) to MAH.

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