The procession of mechanisms is as follows, starting with layer 1:
- calcification
- cross-linking
- vascular smooth muscle dysfunction
Which gives you layer 2:
- vascular stiffness
Which then, entirely and all by itself ( http://dx.doi.org/10.1371/journal.pcbi.1003634 ), causes layer 3 by messing with the feedback mechanisms for blood pressure control:
- hypertension, raised blood pressure
Which then causes layer 4:
- microvascular damage, such as stroke, kidney issues
- major vascular damage and sudden death when combined with atherosclerosis
- cardiac hypertrophy, which is a maladjustment to hypertension
Calcification may be secondary to cellular senescence and other inflammatory mechanisms. Persistent cross-linking may be made worse by dietary sugars, or may not - the better studied forms of sugary by-product are not all that relevant to persistent cross-linking that stiffens tissue. You can read up on glucosepane to learn more about that. The vascular smooth muscle dysfunction is probably caused by a combination of inflammatory mechanisms and everything else that changes with age and poor health, such as metabolic syndrome.
So if thinking about fixing hypertension, you want to be watching people building cross-link breakers, such as the Spiegel team at Yale, funded by the SENS Research Foundation, or people clearing out senescent cells, such as the current brace of senolytic therapy companies, one of which was seed funded by the SENS Research Foundation. Watching the groups looking into smooth muscle may or may not go anywhere; it is very hard to say at this stage whether there is any one target that might help enough for the usual pharmaceutical development approach to work well enough to care about in the near term.